Targeted disruption of Na+/Ca2+ exchanger 3 (NCX3) gene leads to a worsening of ischemic brain damage
Anno: 2008
Rivista: THE JOURNAL OF NEUROSCIENCE
Autori/autrici: Molinaro, Pasquale; Cuomo, Ornella; Pignataro, Giuseppe; Boscia, Francesca; Sirabella, Rossana; Pannaccione, Anna; Secondo, Agnese; Scorziello, Antonella; Adornetto, A; Gala, Rosaria; Viggiano, D; Sokolow, S; Herchuelz, A; Schurmans, S; DI RENZO, GIANFRANCO MARIA LUIGI; Annunziato, Lucio
Lingua: ENG
Classificazione IRIS: 1.1 Articolo in rivista
Scheda completa IRIS: https://iris.univpm.it/handle/11566/337723
Citazioni:
Targeted disruption of Na+/Ca2+ exchanger 3 (NCX3) gene leads to a worsening of ischemic brain damage / Molinaro, P., Cuomo, O., Pignataro, G., Boscia, F., Sirabella, R., Pannaccione, A., Secondo, A., Scorziello, A., Adornetto, A., Gala, R., Viggiano, D., Sokolow, S., Herchuelz, A., Schurmans, S., DI RENZO, G.M.L., Annunziato, L.. - In: THE JOURNAL OF NEUROSCIENCE. - ISSN 0270-6474. - STAMPA. - 28:5(2008), pp. 1179-1184. [10.1523/JNEUROSCI.4671-07.2008]
Abstract:
Na+/Ca+ exchanger 3 (NCX3), one of the three isoforms of the NCX family, is highly expressed in the brain and is involved in the maintenance of intracellular Na+ and Ca2+ homeostasis. Interestingly, whereas the function of NCX3 under physiological conditions has been determined, its role under anoxi...a is still unknown. To assess NCX3 role in cerebral ischemia, we exposed ncx3-/- mice to transient middle cerebral artery occlusion followed by reperfusion. In addition, to evaluate the effect of ncx3 ablation on neuronal survival, organotypic hippocampal cultures and primary cortical neurons from ncx3-/- mice were subjected to oxygen glucose deprivation (OGD) plus reoxygenation. Here we report that ncx3 gene suppression leads to a worsening of brain damage after focal ischemia and to a massive neuronal death in all the hippocampal fields of organotypic cultures as well as in cortical neurons from ncx3-/- mice exposed to OGD plus reoxygenation. In addition, in ncx3-/- cortical neurons exposed to hypoxia, NCX currents, recorded in the reverse mode of operation, were significantly lower than those detected in ncx3+/+. From these results, NCX3 protein emerges as a new molecular target that may have a potential therapeutic value in modulating cerebral ischemia.
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A critical role for the potassium-dependent sodium-calcium exchanger NCKX2 in protection against focal ischemic brain damage
Anno: 2008
Rivista: THE JOURNAL OF NEUROSCIENCE
Autori/autrici: Cuomo, Ornella; Gala, Rosaria; Pignataro, Giuseppe; Boscia, Francesca; Secondo, Agnese; Scorziello, Antonella; Pannaccione, Anna; Viggiano, Davide; Adornetto, Annagrazia; Molinaro, Pasquale; Li, Xf; Lytton, J; DI RENZO, GIANFRANCO MARIA LUIGI; Annunziato, Lucio
Lingua: ENG
Classificazione IRIS: 1.1 Articolo in rivista
Scheda completa IRIS: https://iris.univpm.it/handle/11566/337713
Citazioni:
A critical role for the potassium-dependent sodium-calcium exchanger NCKX2 in protection against focal ischemic brain damage / Cuomo, O., Gala, R., Pignataro, G., Boscia, F., Secondo, A., Scorziello, A., Pannaccione, A., Viggiano, D., Adornetto, A., Molinaro, P., Li, X.f., Lytton, J., DI RENZO, G.M.L., Annunziato, L.. - In: THE JOURNAL OF NEUROSCIENCE. - ISSN 0270-6474. - STAMPA. - 28:9(2008), pp. 2053-2063. [10.1523/JNEUROSCI.4912-07.2008]
Abstract:
The superfamily of cation/Ca2+ plasma-membrane exchangers contains two branches, the K+-independent Na+-Ca2+ exchangers (NCXs) and the K+-dependent Na+-Ca2+ exchangers (NCKXs), widely expressed in mammals. NCKX2 is the major neuronally expressed isoform among NCKX members. Despite its importance in ...maintaining Na+, Ca2+, and K+ homeostasis in the CNS, the role of NCKX2 during cerebral ischemia, a condition characterized by an alteration of ionic concentrations, has not yet been investigated. The present study examines NCKX2 role in the development of ischemic brain damage in permanent middle cerebral artery occlusion (pMCAO) and transient middle cerebral artery occlusion. Furthermore, to evaluate the effect of nckx2 ablation on neuronal survival, nckx2-/- primary cortical neurons were subjected to oxygen glucose deprivation plus reoxygenation. NCKX2 mRNA and protein expression was evaluated in the ischemic core and surrounding ipsilesional areas, at different time points after pMCAO in rats. In ischemic core and in periinfarctual area, NCKX2 mRNA and protein expression were downregulated. In addition, NCKX2 knock-down by antisense oligodeoxynucleotide and NCKX2 knock-out by genetic disruption dramatically increased infarct volume. Accordingly, nckx2-/- primary cortical neurons displayed a higher vulnerability and a greater [Ca2+]i increase under hypoxic conditions, compared with nckx2+/+ neurons. In addition, NCKX currents both in the forward and reverse mode of operation were significantly reduced in nckx2-/- neurons compared with nckx2+/+ cells. Overall, these results indicate that NCKX2 is involved in brain ischemia, and it may represent a new potential target to be investigated in the study of the molecular mechanisms involved in cerebral ischemia.
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The Cu-Zn superoxide dismutase (SOD1) inhibits ERK phosphorylation by muscarinic receptor modulation in rat pituitary GH3 cells
Anno: 2008
Rivista: BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
Autori/autrici: Secondo, Agnese; De Mizio, M; Zirpoli, Laura; Santillo, Mariarosaria; Mondola, Paolo
Lingua: ENG
Classificazione IRIS: 1.1 Articolo in rivista
Scheda completa IRIS: https://iris.univpm.it/handle/11566/337722
Citazioni:
The Cu-Zn superoxide dismutase (SOD1) inhibits ERK phosphorylation by muscarinic receptor modulation in rat pituitary GH3 cells / Secondo, A., De Mizio, M., Zirpoli, L., Santillo, M., Mondola, P.. - In: BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS. - ISSN 0006-291X. - STAMPA. - 376:1(2008), pp. 143-147. [10.1016/j.bbrc.2008.08.110]
Abstract:
The Cu-Zn superoxide dismutase (SOD1) belongs to a family of isoenzymes that are able to dismutate the oxygen superoxide in hydrogen peroxide and molecular oxygen. This enzyme is secreted by many cellular lines and it is also released trough a calcium-dependent depolarization mechanism involving SNA...RE protein SNAP 25. Using rat pituitary GH3 cells that express muscarinic receptors we found that SOD1 inhibits P-ERK1/2 pathway trough an interaction with muscarinic M1 receptor. This effect is strengthened by oxotremorine, a muscarinic M agonist and partially reverted by pyrenzepine, an antagonist of M1 receptor; moreover this effect is independent from increased intracellular calcium concentration induced by SOD1. Finally, P-ERK1/2 inhibition was accompanied by the reduction of GH3 cell proliferation. These data indicate that SOD1 beside the well studied antioxidant properties can be considered as a neuromodulator able to affect mitogen-activated protein kinase in rat pituitary cells trough a M1 muscarinic receptor.
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The two isoforms of the Na+/Ca2+ exchanger, NCX1 and NCX3, constitute novel additional targets for the prosurvival action of Akt/protein kinase B pathway
Anno: 2008
Rivista: MOLECULAR PHARMACOLOGY
Autori/autrici: Formisano, L; Saggese, M; Secondo, Agnese; Sirabella, Rossana; Vito, P; Valsecchi, V; Molinaro, Pasquale; DI RENZO, GIANFRANCO MARIA LUIGI; Annunziato, Lucio
Lingua: ENG
Classificazione IRIS: 1.1 Articolo in rivista
Scheda completa IRIS: https://iris.univpm.it/handle/11566/337746
Citazioni:
The two isoforms of the Na+/Ca2+ exchanger, NCX1 and NCX3, constitute novel additional targets for the prosurvival action of Akt/protein kinase B pathway / Formisano, L., Saggese, M., Secondo, A., Sirabella, R., Vito, P., Valsecchi, V., Molinaro, P., DI RENZO, G.M.L., Annunziato, L.. - In: MOLECULAR PHARMACOLOGY. - ISSN 0026-895X. - STAMPA. - 73:3(2008), pp. 727-737. [10.1124/mol.107.042549]
Abstract:
The proteins NCX1, NCX2, and NCX3 expressed on the plasma membrane of neurons play a crucial role in ionic regulation because they are the major bidirectional system promoting the efflux and influx of Na(+) and Ca(2+) ions. Here, we demonstrate that NCX1 and NCX3 proteins are novel additional target...s for the survival action of the phosphatidylinositol 3-kinase (PI3-K)/Akt pathway. Indeed, the doxycycline-dependent overexpression of constitutively active Akt1 in tetracycline (Tet)-Off PC-12 positive mutants and the exposure of Tet-Off PC-12 wild type to nerve growth factor induced an up-regulation of NCX1 and NCX3 proteins. NCX1 up-regulation induced by Akt1 activation occurred at the transcriptional level because NCX1 mRNA increased, and it was counteracted by cAMP response element-binding protein 1 inhibition through small interfering RNA strategy. In contrast, Akt1-induced NCX3 up-regulation recognized a post-transcriptional mechanism occurring at the proteasome level because 1) NCX3 transcript did not increase and 2) the proteasome inhibitor N-benzyloxycarbonyl (Z)-Leu-Leu-leucinal (MG-132) did not further enhance NCX3 protein levels in Akt1 active mutants as it would be expected if the ubiquitin-proteasome complex was not already blocked by Akt1 pathway. As expected, in PC-12 Tet-Off wild-type cells MG-132 enhanced NCX3 protein levels. This up-regulation produced an increased activity of NCX function. Furthermore, NCX1 and NCX3 up-regulation contributed to the survival action of Akt1 during chemical hypoxia because both the silencing of NCX1 or NCX3 and the pharmacological paninhibition of NCX isoforms reduced the prosurvival property of Akt1. Together, these results indicated that NCX1 and NCX3 represent novel additional molecular targets for the prosurvival action of PI3-K/Akt pathway.
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The Na+/Ca2+ exchanger isoform 3 (NCX3) but not isoform 2 (NCX2) and 1 (NCX1) singly transfected in BHK cells plays a protective role in a model of in vitro hypoxia
Anno: 2007
Rivista: ANNALS OF THE NEW YORK ACADEMY OF SCIENCES
Autori/autrici: Secondo, Agnese; Staiano, ROSARIA ILARIA; Scorziello, Antonella; Sirabella, Rossana; Boscia, Francesca; Adornetto, Annagrazia; Canzoniero, Lm; DI RENZO, GIANFRANCO MARIA LUIGI; Annunziato, Lucio
Lingua: ENG
Classificazione IRIS: 1.1 Articolo in rivista
Scheda completa IRIS: https://iris.univpm.it/handle/11566/337667
Citazioni:
The Na+/Ca2+ exchanger isoform 3 (NCX3) but not isoform 2 (NCX2) and 1 (NCX1) singly transfected in BHK cells plays a protective role in a model of in vitro hypoxia / Secondo, A., Staiano, R.I., Scorziello, A., Sirabella, R., Boscia, F., Adornetto, A., Canzoniero, L.m., DI RENZO, G.M.L., Annunziato, L.. - In: ANNALS OF THE NEW YORK ACADEMY OF SCIENCES. - ISSN 0077-8923. - STAMPA. - 1099:(2007), pp. 481-485. [10.1196/annals.1387.052]
Abstract:
Chemical hypoxia produces depletion of ATP, intracellular Ca2+ overload, and cell death. The role of Na+/Ca2+ exchanger (NCX), the major plasma membrane Ca2+ extruding system, has been explored in chemical hypoxia using BHK cells stably transfected with the three mammalian NCX isoforms: NCX1, NCX2, ...and NCX3. Here we report that the three isoforms show similar activity evaluated as [Ca2+]i increase evoked by Na+-free medium exposure in Fura-2-loaded single cells and NCX3 transfected cells are less vulnerable to chemical hypoxia compared to NCX1- and NCX2-transfected cells, suggesting that NCX3 could play a more relevant protective role during chemical hypoxia.
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Evidence of calcium- and SNARE-dependent release of CuZn superoxide dismutase from rat pituitary GH3 cells and synaptosomes in response to depolarization
Anno: 2007
Rivista: JOURNAL OF NEUROCHEMISTRY
Autori/autrici: Santillo, Mariarosaria; Secondo, Agnese; Serù, R; Damiano, S; Garbi, Corrado; Taverna, E; Rosa, P; Giovedì, S; Benfenati, F; Mondola, Paolo
Lingua: ENG
Classificazione IRIS: 1.1 Articolo in rivista
Scheda completa IRIS: https://iris.univpm.it/handle/11566/337772
Citazioni:
Evidence of calcium- and SNARE-dependent release of CuZn superoxide dismutase from rat pituitary GH3 cells and synaptosomes in response to depolarization / Santillo, M., Secondo, A., Serù, R., Damiano, S., Garbi, C., Taverna, E., Rosa, P., Giovedì, S., Benfenati, F., Mondola, P.. - In: JOURNAL OF NEUROCHEMISTRY. - ISSN 0022-3042. - STAMPA. - 102:3(2007), pp. 679-685. [10.1111/j.1471-4159.2007.04538.x]
Abstract:
The antioxidant enzyme CuZn superoxide dismutase (SOD1) is secreted by many cell lines. However, it is not clear whether SOD1 secretion is only constitutive or can be regulated in an activity-dependent fashion. Using rat pituitary GH(3) cells that express voltage-dependent calcium channels and are s...ubjected to Ca(2+) oscillations, we found that treatment with high K(+)-induced SOD1 release that was significantly higher than the constitutive secretion. Evoked SOD1 release was correlated with depolarization-dependent calcium influx and was virtually abolished by removal of extracellular calcium with EGTA or by pre-incubation of GH(3) cells with Botulinum toxin A that cleaves the SNARE protein SNAP-25. Immunofluorescence experiments performed in GH(3) cells and rat brain synaptosomes showed that K(+)-depolarization induced a marked depletion of intracellular SOD1 immunoreactivity, an effect that was again abolished in the absence of extracellular calcium or after treatment with Botulinum toxin A. Subcellular fractionation analysis showed that SOD1 was present in large dense core vesicles. These data clearly show that, in addition to the constitutive SOD1 secretion, depolarization induces an additional rapid calcium-dependent SOD1 release in GH(3) cells and in rat brain synaptosomes. This likely occurs through exocytosis from SOD1-containing vesicles operated by the SNARE complex
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Differentiation of monocytes into macrophages induces the upregulation of histamine H1 receptor
Anno: 2007
Rivista: JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
Autori/autrici: Triggiani, Massimo; Petraroli, A; Loffredo, S; Frattini, A; Granata, F; Morabito, P; Staiano, R. I.; Secondo, Agnese; Annunziato, Lucio; Marone, Gianni; Loffredo, Stefania
Lingua: ENG
Classificazione IRIS: 1.1 Articolo in rivista
Scheda completa IRIS: https://iris.univpm.it/handle/11566/337770
Citazioni:
Differentiation of monocytes into macrophages induces the upregulation of histamine H1 receptor / Triggiani, M., Petraroli, A., Loffredo, S., Frattini, A., Granata, F., Morabito, P., Staiano, R.I., Secondo, A., Annunziato, L., Marone, G., Loffredo, S.. - In: JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY. - ISSN 0091-6749. - STAMPA. - 119:(2007), pp. 472-481. [10.1016/j.jaci.2006.09.027]
Abstract:
BACKGROUND: Histamine modulates several functions in human monocytes, macrophages, and dendritic cells. However, responses elicited by histamine differ depending on cell type, suggesting variable expression of histamine receptors in the monocyte/macrophage lineage. OBJECTIVE: We sought to examine wh...ether the expression of H(1) receptors was regulated by cell differentiation of human monocytes into macrophages or dendritic cells. METHODS: Expression of H(1) receptor was evaluated by RT-PCR and western blot in monocytes, monocyte-derived macrophages (MDMs), monocyte-derived dendritic cells (DCs) and human lung macrophages (HLMs). RESULTS: Expression of H(1) receptor mRNA and protein was higher in HLMs and DCs than in monocytes. H(1) expression was approximately 15-fold and 4-fold higher in MDMs and HLMs, respectively, as compared with that seen in monocytes. H(1) receptor protein was undetectable in monocytes, whereas it was conspicuous in MDMs. Simultaneous analysis of H(2) and H(1) mRNA expression indicated that the H(2)/H(1) ratio decreased from 202.7 +/- 14.8 in monocytes to 2.2 +/- 0.4 in MDM and 39.5 +/- 5.0 in DCs. Incubation of monocytes with histamine neither affected intracellular Ca(2+) concentrations nor influenced IL-8 production. In contrast, histamine rapidly induced a Ca(2+) signal and stimulated IL-8 production in MDMs. Both effects were inhibited by H(1) blockade with levocetirizine, but not by H(2) blockade with ranitidine. CONCLUSIONS: Differentiation of monocytes into macrophages or dendritic cells is associated with profound changes of histamine receptor expression. Upregulation of H(1) receptors confers on macrophages the capacity of being activated by histamine. CLINICAL IMPLICATIONS: Regulation of H(1) and H(2) receptor expression in the monocyte/macrophage lineage can be relevant to the pathogenesis of allergic inflammation.
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BHK cells transfected with NCX3 are more resistant to hypoxia followed by reoxygenation than those transfected with NCX1 and NCX2: Possible relationship with mitochondrial membrane potential
Anno: 2007
Rivista: CELL CALCIUM
Autori/autrici: Secondo, Agnese; Staiano, ROSARIA ILARIA; Scorziello, Antonella; Sirabella, Rossana; Boscia, Francesca; Adornetto, Annagrazia; Valsecchi, Valeria; Molinaro, Pasquale; Canzoniero, Lm; DI RENZO, GIANFRANCO MARIA LUIGI; Annunziato, Lucio
Lingua: ENG
Classificazione IRIS: 1.1 Articolo in rivista
Scheda completa IRIS: https://iris.univpm.it/handle/11566/337747
Citazioni:
BHK cells transfected with NCX3 are more resistant to hypoxia followed by reoxygenation than those transfected with NCX1 and NCX2: Possible relationship with mitochondrial membrane potential / Secondo, A., Staiano, R.I., Scorziello, A., Sirabella, R., Boscia, F., Adornetto, A., Valsecchi, V., Molinaro, P., Canzoniero, L.m., DI RENZO, G.M.L., Annunziato, L.. - In: CELL CALCIUM. - ISSN 0142-8020. - STAMPA. - 42:6(2007), pp. 521-535. [10.1016/j.ceca.2007.01.006]
Abstract:
The specific role played by NCX1, NCX2, and NCX3, the three isoforms of the Na+/Ca2+ exchanger (NCX), has been explored during hypoxic conditions in BHK cells stably transfected with each of these isoforms. Six major findings emerged from the present study: (1) all the three isoforms were highly exp...ressed on the plasma membranes of BHK cells; (2) under physiological conditions, the three NCX isoforms showed similar functional activity; (3) hypoxia plus reoxygenation induced a lower increase of [Ca2+]i in BHK-NCX3-transfected cells than in BHK-NCX1- and BHK-NCX2-transfected cells; (4) NCX3-transfected cells were more resistant to chemical hypoxia plus reoxygenation than NCX1- and NCX2-transfected cells. Interestingly, such augmented resistance was eliminated by CBDMD (10 μM), an inhibitor of NCX and by the specific silencing of the NCX3 isoform; (5) chemical hypoxia plus reoxygenation produced a loss of mitochondrial membrane potential in NCX1- and NCX2-transfected cells, but not in NCX3-transfected cells; (6) the forward mode of operation in NCX3-transfected cells was not affected by ATP depletion, as it occurred in NCX1- and NCX2-transfected cells. Altogether, these results indicate that the brain specifically expressed NCX3 isoform more significantly contributes to the maintenance of [Ca2+]i homeostasis during experimental conditions mimicking ischemia, thereby preventing mitochondrial Δψ collapses and cell death.
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Glutamate-independent calcium toxicity: introduction
Anno: 2007
Rivista: STROKE
Autori/autrici: Annunziato, Lucio; Cataldi, Mauro; Pignataro, Giuseppe; Secondo, Agnese; Molinaro, Pasquale
Lingua: ENG
Classificazione IRIS: 1.1 Articolo in rivista
Scheda completa IRIS: https://iris.univpm.it/handle/11566/337753
Citazioni:
Glutamate-independent calcium toxicity: introduction / Annunziato, L., Cataldi, M., Pignataro, G., Secondo, A., Molinaro, P.. - In: STROKE. - ISSN 0039-2499. - STAMPA. - 38:2 Suppl(2007), pp. 661-664. [10.1161/01.STR.0000247942.42349.37]
Abstract:
t is widely accepted that a critical factor in determining neuronal death during cerebral ischemia is the progressive accumulation of intracellular Na+ ([Na+]i) and Ca2+ ([Ca2+]i) ions, which can precipitate necrosis and apoptosis of vulnerable neurons. Whereas the detrimental action of [Na+]i incre...ase is attributable to both cell swelling and microtubular disorganization—2 phenomena that lead to cell necrosis1—a change in [Ca2+]i has been shown to be a key factor in ischemic brain damage, for it modulates several death pathways, including oxidative and nitrosative stress, mitochondrial dysfunction, and protease activation.
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ncx1, ncx2, and ncx3 gene product expression and function in neuronal anoxia and brain ischemia
Anno: 2007
Rivista: ANNALS OF THE NEW YORK ACADEMY OF SCIENCES
Autori/autrici: Annunziato, Lucio; Pignataro, Giuseppe; Boscia, Francesca; Sirabella, Rossana; Formisano, Luigi; Saggese, Mariangela; Cuomo, Ornella; Gala, Rosaria; Secondo, Agnese; Viggiano, Davide; Molinaro, Pasquale; Valsecchi, Valeria; Tortiglione, Anna; Adornetto, Annagrazia; Scorziello, Antonella; Cataldi, Mauro; DI RENZO, GIANFRANCO MARIA LUIGI
Lingua: ENG
Classificazione IRIS: 1.1 Articolo in rivista
Scheda completa IRIS: https://iris.univpm.it/handle/11566/337738
Citazioni:
ncx1, ncx2, and ncx3 gene product expression and function in neuronal anoxia and brain ischemia / Annunziato, L., Pignataro, G., Boscia, F., Sirabella, R., Formisano, L., Saggese, M., Cuomo, O., Gala, R., Secondo, A., Viggiano, D., Molinaro, P., Valsecchi, V., Tortiglione, A., Adornetto, A., Scorziello, A., Cataldi, M., DI RENZO, G.M.L.. - In: ANNALS OF THE NEW YORK ACADEMY OF SCIENCES. - ISSN 0077-8923. - STAMPA. - 1099:(2007), pp. 413-426. [10.1196/annals.1387.050]
Abstract:
Over the last few years, although extensive studies have focused on the relevant function played by the sodium–calcium exchanger (NCX) during focal ischemia, a thorough understanding of its role still remains a controversial issue. We explored the consequences of the pharmacological inhibition... of this antiporter with conventional pharmacological approach, with the synthetic inhibitory peptide, XIP, or with an antisense strategy on the extent of brain damage induced by the permanent occlusion of middle cerebral artery (pMCAO) in rats. Collectively, the results of these studies suggest that ncx1 and ncx3 genes could be play a major role to limit the severity of ischemic damage probably as they act to dampen [Na+]i and [Ca2+]i overload. This mechanism seems to be normally activated in the ischemic brain as we found a selective upregulation of NCX1 and NCX3 mRNA levels in regions of the brain surviving to an ischemic insult. Despite this transcript increase, NCX1, NCX2, and NCX3 proteins undergo an extensive proteolytic degradation in the ipsilateral cerebral hemisphere. All together these results suggest that a rescue program centered on an increase NCX function and expression could halt the progression of the ischemic damage. On the basis of this evidence we directed our attention to the understanding of the transductional and transcriptional pathways responsible for NCX upregulation. To this aim, we are studying whether the brain isoform of Akt, Akt1, which is a downstream effector of neurotrophic factors, such as NGF can, in addition to affecting the other prosurvival cascades, also exert its neuroprotective effect by modulating the expression and activity of ncx1, ncx2, and ncx3 gene products.
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Profarmaci dell’arginina con elevata attività terapeutica
Anno: 2006
Autori/autrici: Annunziato, Lucio; Secondo, Agnese; Minale, M; Melisi, D; Rimoli, Mg; Montoro, P; Piacente, S; De Capraris, P.
Classificazione IRIS: 6.1 Brevetto
Scheda completa IRIS: https://iris.univpm.it/handle/11566/337661
Citazioni:
Profarmaci dell’arginina con elevata attività terapeutica / Annunziato, L., Secondo, A., Minale, M., Melisi, D., Rimoli, M.g., Montoro, P., Piacente, S., De Capraris, P.. - (2006).
Abstract:
La presente invenzione riguarda il campo dei profarmaci, utili nel trattamento delle disfunzioni endoteliali e di ogni altra patologia causata da una ridotta disponibilità di arginina e/o di monossido d’azoto. L’Arginina è considerata l’unico precursore fisiologico pe...r la formazione di NO. Essa è classificata come aminoacido semi-essenziale essendo parzialmente assorbita dalla dieta e parzialmente sintetizzata de novo nell’adulto sano (Nutr. Rev. 1976, 34, 307-9; J. parent. Ent. Nutr. 1986, 10, 227-238). Si descrivono esteri dell’arginina (enantiomeri L- e/o D-) con D-galattosio utili come profarmaci dotati di elevata capacità di penetrazione attraverso le membrane cellulari e la barriera ematoencefalica. Gli esteri dell’invenzione, una volta assorbiti, rilasciano gradualmente l’arginina ed assicurano livelli di farmaco prolungati e elevati, generando una risposta terapeutica consistente e prolungata nel tempo. Ulteriori descrizioni Senza limitazione alcuna, ogni malattia che trae beneficio dal trattamento con arginina, è vantaggiosamente trattabile anche con i presenti esteri, i quali permettono una maggiore accessibilità dell’aminoacido nei comparti dell’organismo posti oltre le membrane cellulari e/o la BEE. Gli esteri dell’invenzione sono in grado di attraversare le membrane cellulari e la BEE sfruttando i sistemi di trasporto transmembranali specifici per gli aminoacidi cationici (Y+, B0,+, b0,+ e Y+L). Da un punto di vista tecnico, le metodologie utilizzate per l’ottenimento di questi risultati comprendono sintesi organica, NMR, HPLC-massa, colture cellulari, microscopia convenzionale e confocale. L’esterificazione con galattosio ha permesso l’ottenimento di una maggiore concentrazione di arginina a livello intracellulare e del SNC, facilitandone il passaggio attraverso le membrane plasmatiche e la BEE. Le malattie trattabili con gli esteri della presente invenzione sono in particolare le seguenti. Disfunzioni endoteliali, intendendo con tale termine ogni patologia caratterizzata da una alterata funzionalità dell’endotelio. Esempi di tali disfunzioni sono: insufficienza cardiaca congestizia, aterosclerosi, sindromi coronariche acute, angina pectoris, scompenso cardiaco cronico, ipertensione arteriosa (essenziale, reno-vascolare, gravidica o preclampsia, portale, ecc.). Altre malattie che possono vantaggiosamente essere trattate con gli esteri dell’invenzione sono: diabete, iperammoniemia da insufficienza epatica, disfunzioni erettili, dispermie seminali, in particolare quelle in presenza di oligoastenospermia, oligozoospermia e bradicinesi, patologie collegate ad una ridotta disponibilità di ormone della crescita (ad es. deficit della crescita), patologie collegate ad una ridotta disponibilità di poliamine cerebrali, patologie neurodegenerative quali il Morbo di Alzheimer, il morbo di Parkinson e l’ictus cerebrale, ecc. Grazie all’attività elevata e prolungata nel tempo dei presenti esteri, si è ottenuto il vantaggio di evitare somministrazioni di arginina in dosaggi particolarmente elevati, e/o ripetute a breve frequenza nel tempo, con particolare vantaggio per quei trattamenti di carattere curativo o preventivo che richiedono una terapia prolungata. Inoltre, il superamento della BEE ha permesso di sfruttare efficacemente le azioni dell’arginina per patologie a carico del sistema nervoso centrale e periferico, evitando complicate e fastidiose procedure di somministrazione in-situ. Ulteriore oggetto dell’invenzione sono composizioni farmaceutiche, utili per il trattamento di patologie che beneficiano del trattamento con arginina, caratterizzate dal contenere un estere di arginina e D-galattosio.
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Galactosyl derivatives of L-arginine and D-arginine: synthesis, stability, cell permeation, and nitric oxide production in pituitary GH3 cells
Anno: 2006
Rivista: JOURNAL OF MEDICINAL CHEMISTRY
Autori/autrici: Melisi, Daniela; Secondo, Agnese; Montoro, P; Piacente, S; Rimoli, MARIA GRAZIA; Minale, Massimiliano; DE CAPRARIIS, Paolo; Annunziato, Lucio
Lingua: ENG
Classificazione IRIS: 1.1 Articolo in rivista
Scheda completa IRIS: https://iris.univpm.it/handle/11566/337760
Citazioni:
Galactosyl derivatives of L-arginine and D-arginine: synthesis, stability, cell permeation, and nitric oxide production in pituitary GH3 cells / Melisi, D., Secondo, A., Montoro, P., Piacente, S., Rimoli, M.G., Minale, M., DE CAPRARIIS, P., Annunziato, L.. - In: JOURNAL OF MEDICINAL CHEMISTRY. - ISSN 0022-2623. - STAMPA. - 49:16(2006), pp. 4826-4833. [10.1021/jm060005s]
Abstract:
Nitric oxide (NO) is critical for the normal physiological regulation of the nervous system and other tissues. L-Arginine, but not D-arginine, is the natural substrate for nitric oxide synthase (NOS), for it is enzymatically converted to NO and L-citrulline. However, recent evidence suggests that D-...arginine can also produce NO and NO-derivatives via a different pathway. The aim of the present paper was to raise NO levels in the cells by increasing the cell permeation of its precursors. To this aim, two galactosyl prodrugs, L-arginine-D-galactos-6'-yl ester (L-ArgGal) and D-arginine-D-galactos-6'-yl ester (D-ArgGal) were synthesized. Remarkably, using the HPLC-ESI/MS technique, we found that L-ArgGal and D-ArgGal prodrugs both increased the concentration levels of L- and D-arginine and their derivatives in pituitary GH3 cells. Furthermore, we found that D-ArgGal (1) penetrated cell membranes more rapidly than its precursor D-arginine, (2) released arginine more slowly and in greater amounts than L-ArgGal, and (3) produced much higher levels of DAF-2 monitored NO and nitrite than did L-ArgGal under the same experimental conditions. In conclusion, these results indicate that an increase in the cell permeation of L- and D-arginine by L-ArgGal and D-ArgGal can lead to an increase in NO levels.
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Nitric oxide induces [Ca2+]i oscillations in pituitary GH3 cells: involvement of IDR and ERG K+ currents
Anno: 2006
Rivista: AMERICAN JOURNAL OF PHYSIOLOGY. CELL PHYSIOLOGY
Autori/autrici: Secondo, Agnese; Pannaccione, Anna; Cataldi, Mauro; Sirabella, Rossana; Formisano, Luigi; DI RENZO, GIANFRANCO MARIA LUIGI; Annunziato, Lucio
Lingua: ENG
Classificazione IRIS: 1.1 Articolo in rivista
Scheda completa IRIS: https://iris.univpm.it/handle/11566/337665
Citazioni:
Nitric oxide induces [Ca2+]i oscillations in pituitary GH3 cells: involvement of IDR and ERG K+ currents / Secondo, A., Pannaccione, A., Cataldi, M., Sirabella, R., Formisano, L., DI RENZO, G.M.L., Annunziato, L.. - In: AMERICAN JOURNAL OF PHYSIOLOGY. CELL PHYSIOLOGY. - ISSN 0363-6143. - STAMPA. - 290:1(2006), pp. C233-C243. [10.1152/ajpcell.00231.2005]
Abstract:
The role of nitric oxide (NO) in the occurrence of intracellular Ca2+ concentration ([Ca2+]i) oscillations in pituitary GH3 cells was evaluated by studying the effect of increasing or decreasing endogenous NO synthesis with L-arginine and nitro-L-arginine methyl ester (L-NAME), respectively. When NO... synthesis was blocked with L-NAME (1 mM) [Ca2+]i, oscillations disappeared in 68% of spontaneously active cells, whereas 41% of the quiescent cells showed [Ca2+]i oscillations in response to the NO synthase (NOS) substrate L-arginine (10 mM). This effect was reproduced by the NO donors NOC-18 and S-nitroso-N-acetylpenicillamine (SNAP). NOC-18 was ineffective in the presence of the L-type voltage-dependent Ca2+ channels (VDCC) blocker nimodipine (1 microM) or in Ca2+-free medium. Conversely, its effect was preserved when Ca2+ release from intracellular Ca2+ stores was inhibited either with the ryanodine-receptor blocker ryanodine (500 microM) or with the inositol 1,4,5-trisphosphate receptor blocker xestospongin C (3 microM). These results suggest that NO induces the appearance of [Ca2+]i oscillations by determining Ca2+ influx. Patch-clamp experiments excluded that NO acted directly on VDCC but suggested that NO determined membrane depolarization because of the inhibition of voltage-gated K+ channels. NOC-18 and SNAP caused a decrease in the amplitude of slow-inactivating (IDR) and ether-à-go-go-related gene (ERG) hyperpolarization-evoked, deactivating K+ currents. Similar results were obtained when GH3 cells were treated with L-arginine. The present study suggests that in GH3 cells, endogenous NO plays a permissive role for the occurrence of spontaneous [Ca2+]i oscillations through an inhibitory effect on IDR and on IERG.
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Involvement of the nitric oxide/protein kinase G pathway in polychlorinated biphenyl-induced cell death in SH-SY 5Y neuroblastoma cells.
Anno: 2006
Rivista: JOURNAL OF NEUROSCIENCE RESEARCH
Autori/autrici: Canzoniero, L. M.; Adornetto, A; Secondo, A; Magi, Simona; Dell'Aversano, C; Scorziello, A; Amoroso, Salvatore; DI RENZO, G.
Lingua: ENG
Classificazione IRIS: 1.1 Articolo in rivista
Scheda completa IRIS: https://iris.univpm.it/handle/11566/25979
Citazioni:
Involvement of the nitric oxide/protein kinase G pathway in polychlorinated biphenyl-induced cell death in SH-SY 5Y neuroblastoma cells / Canzoniero, L.M., Adornetto, A., Secondo, A., Magi, S., Dell'Aversano, C., Scorziello, A., Amoroso, S., DI RENZO, G.. - In: JOURNAL OF NEUROSCIENCE RESEARCH. - ISSN 0360-4012. - STAMPA. - 84:(2006), pp. 692-697. [10.1002/jnr.20971]
Abstract:
Abstract. Polychlorinated biphenyls (PCB) are persistent environmental contaminants whose chronic exposure can affect nervous system development and function. The cellular and molecular mechanisms underlying neuronal damage are not yet clear. In the present study, we investigated whether nitric o...xide (NO) could be involved in aroclor 1254 (A1254; a PCB mixture)-induced cytotoxicity in SH-SY5Y human neuroblastoma cells. Prolonged exposure (24 hr) to A1254 (10-100 microg/ml) caused a dose-dependent reduction of cell viability that was attenuated in the presence of a calcium entry blocker, gadolinum (Gd(3+)) at 10 microM, a concentration able to block voltage-sensitive calcium channels. In addition, A1254 caused an increase of cytosolic calcium that was dependent on extracellular calcium, as measured by fura-2 videomicroscopy. A1254-induced calcium rise may stimulate NO production through an activation of neuronal NOS (nNOS). Indeed, the concomitant addition of the selective nNOS inhibitor N(omega)-propyl-L-arginine (NPLA) and A1254 prevented cell injury, suggesting that NO production plays a major role in A1254-evoked cell injury. Furthermore, the exposure (14 hr) to A1254 (30 microg/ml) produced an up-regulation of the expression of beta isoform of nNOS. This up-regulation was calcium dependent and was accompanied by an enhancement of NO production as demonstrated by an increase of nitrite formation. Moreover, A1254-induced cell injury was prevented when KT 5823, a selective cGMP/PKG inhibitor, was added concomitantly to 30 microg/ml A1254. These results suggest that PCB-induced cell death in neuroblastoma cells is mediated by an activation of the cGMP/PKG pathway triggered by NO production.
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Nuclear Factor-kappaB activation by reactive oxygen species mediates voltage-gated K+ current enhancement by neurotoxic beta-amyloid peptides in nerve growth factor-differentiated PC-12 cells and hippocampal neurones
Anno: 2005
Rivista: JOURNAL OF NEUROCHEMISTRY
Autori/autrici: Pannaccione, Anna; Secondo, Agnese; Scorziello, Antonella; Calì, G; Taglialatela, Maurizio; Annunziato, Lucio
Lingua: ENG
Classificazione IRIS: 1.1 Articolo in rivista
Scheda completa IRIS: https://iris.univpm.it/handle/11566/337730
Citazioni:
Nuclear Factor-kappaB activation by reactive oxygen species mediates voltage-gated K+ current enhancement by neurotoxic beta-amyloid peptides in nerve growth factor-differentiated PC-12 cells and hippocampal neurones / Pannaccione, A., Secondo, A., Scorziello, A., Calì, G., Taglialatela, M., Annunziato, L.. - In: JOURNAL OF NEUROCHEMISTRY. - ISSN 0022-3042. - STAMPA. - 94:3(2005), pp. 572-586. [10.1111/j.1471-4159.2005.03075.x]
Abstract:
Increased activity of plasma membrane K+ channels, leading to decreased cytoplasmic K+ concentrations, occurs during neuronal cell death. In the present study, we showed that the neurotoxic beta-amyloid peptide Abeta(25-35) caused a dose-dependent (0.1-10 microm) and time-dependent (> 12 h) enhan...cement of both inactivating and non-inactivating components of voltage-dependent K+ (VGK) currents in nerve growth factor-differentiated rat phaeochromocytoma (PC-12) cells and primary rat hippocampal neurones. Similar effects were exerted by Abeta(1-42), but not by the non-neurotoxic Abeta(35-25) peptide. Abeta(25-35) and Abeta(1-42) caused an early (15-20 min) increase in intracellular Ca(2+) concentration. This led to an increased production of reactive oxygen species (ROS), which peaked at 3 h and lasted for 24 h; ROS production seemed to trigger the VGK current increase as vitamin E (50 microm) blocked both the Abeta(25-35)- and Abeta(1-42)-induced ROS increase and VGK current enhancement. Inhibition of protein synthesis (cycloheximide, 1 microg/mL) and transcription (actinomycin D, 50 ng/mL) blocked Abeta(25-35)-induced VGK current enhancement, suggesting that this potentiation is mediated by transcriptional activation induced by ROS. Interestingly, the specific nuclear factor-kappaB inhibitor SN-50 (5 microm), but not its inactive analogue SN-50M (5 microm), fully counteracted Abeta(1-42)- or Abeta(25-35)-induced enhancement of VGK currents, providing evidence for a role of this family of transcription factors in regulating neuronal K+ channel function during exposure to Abeta.
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The antiepileptic drug Levetiracetam decreases the IP3-Dependent [Ca2+]i increase induced by ATP and BK in PC12 cells
Anno: 2005
Rivista: JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
Autori/autrici: Cataldi, M; Lariccia, Vincenzo; Secondo, A; DI RENZO, G; Annunziato, L.
Lingua: ENG
Classificazione IRIS: 1.1 Articolo in rivista
Scheda completa IRIS: https://iris.univpm.it/handle/11566/39199
Citazioni:
The antiepileptic drug Levetiracetam decreases the IP3-Dependent [Ca2+]i increase induced by ATP and BK in PC12 cells / Cataldi, M., Lariccia, V., Secondo, A., DI RENZO, G., Annunziato, L.. - In: THE JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS. - ISSN 0022-3565. - 313:(2005), pp. 720-730. [10.1124/jpet.104.079327]
Abstract:
The present study explores the hypothesis that the new antiepileptic drug levetiracetam (LEV) could interfere with the inositol 1,4,5-trisphosphate (IP3)-dependent release of intracellular Ca2+ initiated by G(q)-coupled receptor activation, a process that plays a role in triggering and maintaining s...eizures. We assessed the effect of LEV on the amplitude of [Ca2+](i) response to bradykinin (BK) and ATP in single Fura-2/acetoxymethyl ester-loaded PC12 rat pheochromocytoma cells, which express very high levels of LEV binding sites. LEV dose-dependently reduced the [Ca2+](i) increase, elicited either by 1 mu M BK or by 100 mu M ATP (IC50, 0.39 +/- 0.01 mu M for BK and 0.20 +/- 0.01 mu M for ATP; Hill coefficients, 1.33 +/- 0.04 for BK and 1.38 +/- 0.06 for ATP). Interestingly, although the discharge of ryanodine stores by a process of calcium-induced calcium release also took place as part of the [Ca2+](i) response to BK, LEV inhibitory effect was mainly exerted on the IP3-dependent stores. In fact, the drug was still effective after the pharmacological blockade of ryanodine receptors. Furthermore, LEV did not affect Ca2+ stored in the intracellular deposits since it did not reduce the amplitude of [Ca2+](i) response either to thapsigargin or to ionomycin. In conclusion, LEV inhibits Ca2+ release from the IP3-sensitive stores without reducing Ca2+ storage into these deposits. Because of the relevant implications of IP3-dependent Ca2+ release in neuron excitability and epileptogenesis, this novel effect of LEV could provide a useful insight into the mechanisms underlying its antiepileptic properties.
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Evidence for a protective role played by the Na+/Ca2+ exchanger in cerebral ischemia induced by middle cerebral artery occlusion in male rats
Anno: 2004
Rivista: NEUROPHARMACOLOGY
Autori/autrici: Pignataro, G.; Tortiglione, A.; Scorziello, A.; Giaccio, L.; Secondo, A.; Severino, B.; Santagada, V.; Caliendo, G.; Amoroso, Salvatore; DI RENZO, G.; Annunziato, L.
Classificazione IRIS: 1.1 Articolo in rivista
Scheda completa IRIS: https://iris.univpm.it/handle/11566/26340
Citazioni:
Evidence for a protective role played by the Na+/Ca2+ exchanger in cerebral ischemia induced by middle cerebral artery occlusion in male rats / Pignataro, G.; Tortiglione, A.; Scorziello, A.; Giaccio, L.; Secondo, A.; Severino, B.; Santagada, V.; Caliendo, G.; Amoroso, Salvatore; DI RENZO, G.; Annunziato, L.. - In: NEUROPHARMACOLOGY. - ISSN 0028-3908. - 46:(2004), pp. 439-448.

CuZn Superoxide dismutase increases intracellular calcium levels via phospholipase C-protein Kinase C pathway in SK-N-BE cells
Anno: 2004
Rivista: BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
Autori/autrici: Mondola, Paolo; Santillo, Mariarosaria; R., Seru'; S., Damiano; C., Alvino; Ruggiero, Giuseppina; Formisano, Pietro; G., Terrazzano; Secondo, Agnese; Annunziato, Lucio
Lingua: ENM
Classificazione IRIS: 1.1 Articolo in rivista
Scheda completa IRIS: https://iris.univpm.it/handle/11566/337749
Citazioni:
CuZn Superoxide dismutase increases intracellular calcium levels via phospholipase C-protein Kinase C pathway in SK-N-BE cells / Mondola, P., Santillo, M., R., S., S., D., C., A., Ruggiero, G., Formisano, P., G., T., Secondo, A., Annunziato, L.. - In: BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS. - ISSN 0006-291X. - STAMPA. - 324(2):(2004), pp. 887-892.

nNOS activation during oxygen and glucose deprivation triggers cerebellar granule cell death in the later reoxygenation phase
Anno: 2004
Rivista: JOURNAL OF NEUROSCIENCE RESEARCH
Autori/autrici: Scorziello, A.; Pellegrini, C.; Secondo, A.; Sirabella, R.; Formisano, L.; Sibaud, L.; Amoroso, Salvatore; DI RENZO, G.; Annunziato, L.
Classificazione IRIS: 1.1 Articolo in rivista
Scheda completa IRIS: https://iris.univpm.it/handle/11566/26346
Citazioni:
nNOS activation during oxygen and glucose deprivation triggers cerebellar granule cell death in the later reoxygenation phase / Scorziello, A., Pellegrini, C., Secondo, A., Sirabella, R., Formisano, L., Sibaud, L., Amoroso, S., DI RENZO, G., Annunziato, L.. - In: JOURNAL OF NEUROSCIENCE RESEARCH. - ISSN 0360-4012. - 76:(2004), pp. 812-821.

Evidence for a protective role played by Na+-Ca2+ exchanger in cerebral ischemia induced by middle cerebral artery occlusion in male rats
Anno: 2004
Rivista: NEUROPHARMACOLOGY
Autori/autrici: Pignataro, Giuseppe; Tortiglione, Anna; Scorziello, Antonella; Giaccio, A; Secondo, Agnese; Severino, Beatrice; Santagada, Vincenzo; Caliendo, Giuseppe; Amoroso, Salvatore; DI RENZO, GIANFRANCO MARIA LUIGI; Annunziato, Lucio
Lingua: ENG
Classificazione IRIS: 1.1 Articolo in rivista
Scheda completa IRIS: https://iris.univpm.it/handle/11566/337742
Citazioni:
Evidence for a protective role played by Na+-Ca2+ exchanger in cerebral ischemia induced by middle cerebral artery occlusion in male rats / Pignataro, G., Tortiglione, A., Scorziello, A., Giaccio, A., Secondo, A., Severino, B., Santagada, V., Caliendo, G., Amoroso, S., DI RENZO, G.M.L., Annunziato, L.. - In: NEUROPHARMACOLOGY. - ISSN 0028-3908. - STAMPA. - 46:3(2004), pp. 439-448. [10.1016/j.neuropharm.2003.09.015]
Abstract:
In the present paper, the role played by Na+/Ca2+ exchanger (NCX) in focal cerebral ischemia was investigated. To this aim, permanent middle cerebral artery occlusion (pMCAO) was performed in male rats. The effects on the infarct volume of some inhibitors, such as tyrosine-6 glycosylated form of the... exchanger inhibitory peptide (GLU-XIP), benzamil derivative (CB-DMB) and diarylaminopropylamine derivative (bepridil), and of the NCX activator, FeCl3, were examined. FeCl3, CB-DMB, bepridil and GLU-XIP, a modified peptide synthesized in our laboratory in order to facilitate its entrance into the cells through the glucose transporter, were intracerebroventricularly (i.c.v.) infused. FeCl3 (10 microg/kg) was able to reduce the extension of brain infarct volume. This effect was counteracted by the concomitant icv administration of CB-DMB (120 microg/kg). All NCX inhibitors, GLU-XIP, CB-DMB and bepridil, caused a worsening of the brain infarct lesion. These results suggest that a stimulation of NCX activity may help neurons and glial cells that are not irreversibly damaged in the penumbral zone to survive, whereas its pharmacological blockade can compromise their survival.
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TSH/cAMP up-regulate sarco/endoplasmic reticulum Ca2+-ATPases expression and activity in PC Cl3 thyroid cells
Anno: 2004
Rivista: EUROPEAN JOURNAL OF ENDOCRINOLOGY
Autori/autrici: Ulianich, Luca; Secondo, Agnese; De Micheli, S; Treglia, S; Pacifico, FRANCESCO MARIA; Liguoro, D; Moscato, F; Marsigliante, S; Annunziato, Lucio; Formisano, Silvestro; Consiglio, Eduardo; Di Jeso, B.
Lingua: ENG
Classificazione IRIS: 1.1 Articolo in rivista
Scheda completa IRIS: https://iris.univpm.it/handle/11566/337680
Citazioni:
TSH/cAMP up-regulate sarco/endoplasmic reticulum Ca2+-ATPases expression and activity in PC Cl3 thyroid cells / Ulianich, L., Secondo, A., De Micheli, S., Treglia, S., Pacifico, F.M., Liguoro, D., Moscato, F., Marsigliante, S., Annunziato, L., Formisano, S., Consiglio, E., Di Jeso, B.. - In: EUROPEAN JOURNAL OF ENDOCRINOLOGY. - ISSN 0804-4643. - STAMPA. - 150:6(2004), pp. 851-861. [10.1530/eje.0.1500851]
Abstract:
OBJECTIVE: We recently reported that the sarco/endoplasmic reticulum Ca2+-ATPase (SERCA) 2b is the SERCA form preferentially expressed in rat thyroid. Moreover, SERCA2b expression dramatically decreases in virally transformed, highly tumorigenic, PC Cl3 thyroid cells. These results suggest that, in ...the thyroid, SERCA2b, in addition to its housekeeping role, is linked to differentiation and is a regulated gene. We therefore sought to study the effect of TSH, the main regulator of thyroid function, on SERCA2b expression and activity. METHODS: PC Cl3 cells were hormone starved in low-serum medium and stimulated for long (48 h) or short (1, 2 and 4 h) times. SERCA2b expression and activity were evaluated by Northern and Western blots, Ca2+-ATPase activity and Ca2+ store content. RESULTS: In PC Cl3 cells, SERCA2b mRNA and protein were induced twofold by a 48-h long treatment with TSH. Long-term elevation (48 h) of intracellular cAMP levels, by forskolin or 8-Br-cAMP, had similar effects on SERCA2b mRNA and protein. We also measured Ca2+-ATPase activity and Ca2+ store content. Both long (48 h) and short (0.5-1 h) treatments with TSH, forskolin or 8-Br-cAMP induced a marked increase of SERCA2b activity. This effect was completely abolished by H89, a specific inhibitor of cAMP-dependent protein kinase A (PKA). TSH and 8-Br-cAMP increased Ca2+ store content after both long (48 h) and short (1-2 h) treatments. CONCLUSIONS: These data suggested that TSH/cAMP acts as an important regulator of both SERCA2b expression and activity in the thyroid system, through PKA activation.
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First- and Second-generation H1 antihistamines: from the molecular basis of their interaction with HERG K+ channels to physiological and pathophysiological implication
Anno: 2004
Autori/autrici: M., Taglialatela; Castaldo, Pasqualina; A., Pannaccione; A., Secondo; M., Cataldi; F., Boscia; L., Annunziato
Classificazione IRIS: 2.1 Contributo in volume (Capitolo o Saggio)
Scheda completa IRIS: https://iris.univpm.it/handle/11566/128662
Citazioni:
First- and Second-generation H1 antihistamines: from the molecular basis of their interaction with HERG K+ channels to physiological and pathophysiological implication / M., T., Castaldo, P., A., P., A., S., M., C., F., B., L., A.. - 4:(2004), pp. 183-190.

Cu,Zn superoxide dismutase increases intracellular calcium levels via a phospholipase C-protein kinase C pathway in SK-N-BE neuroblastoma cells
Anno: 2004
Rivista: BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
Autori/autrici: Mondola, Paolo; Santillo, Mariarosaria; Serù, R; Damiano, S; Alvino, C; Ruggiero, Giuseppina; Formisano, Pietro; Terrazzano, G; Secondo, Agnese; Annunziato, L.
Lingua: ENG
Classificazione IRIS: 1.1 Articolo in rivista
Scheda completa IRIS: https://iris.univpm.it/handle/11566/337677
Citazioni:
Cu,Zn superoxide dismutase increases intracellular calcium levels via a phospholipase C-protein kinase C pathway in SK-N-BE neuroblastoma cells / Mondola, P., Santillo, M., Serù, R., Damiano, S., Alvino, C., Ruggiero, G., Formisano, P., Terrazzano, G., Secondo, A., Annunziato, L.. - In: BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS. - ISSN 0006-291X. - STAMPA. - 324:2(2004), pp. 887-892. [10.1016/j.bbrc.2004.09.131]
Abstract:
The superoxide dismutase isoenzymes (SOD) play a key role in scavenging, O*2- radicals. In contrast with previous studies, recent data have shown that human neuroblastoma cells are able to export the cytosolic Cu,Zn superoxide dismutase (SOD1), thus suggesting a paracrine role exerted by this enzyme... in the nervous system. To evaluate whether SOD1 could activate intracellular signalling pathways, the functional interaction between SOD1 and human neuroblastoma SK-N-BE cells was investigated. By analyzing the surface binding of biotinylated SOD1 on SK-N-BE cells and by measuring intracellular calcium concentrations and PKC activity, we demonstrated that SOD1 specifically interacts in a dose-dependent manner with the cell surface membrane of SK-N-BE. This binding was able to activate a PLC-PKC-dependent pathway that increased intracellular calcium concentrations mainly deriving from the intracellular stores. Furthermore, we showed that this effect was independent of SOD1 dismutase activity and was totally inhibited by U73122, the PLC blocker. On the whole, these data indicate that SOD1 carries out a neuromodulatory role affecting calcium-dependent cellular functions.
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Neuronal NOS activation during oxygen and glucose deprivation triggers cerebellar granule cell death in the later reoxygenation phase
Anno: 2004
Rivista: JOURNAL OF NEUROSCIENCE RESEARCH
Autori/autrici: Scorziello, Antonella; Pellegrini, C; Secondo, Agnese; Sirabella, Rossana; Formisano, Luigi; Sibaud, L; Amoroso, Salvatore; Canzoniero, Lmt; Annunziato, Lucio; DI RENZO, GIANFRANCO MARIA LUIGI
Lingua: ENG
Classificazione IRIS: 1.1 Articolo in rivista
Scheda completa IRIS: https://iris.univpm.it/handle/11566/337717
Citazioni:
Neuronal NOS activation during oxygen and glucose deprivation triggers cerebellar granule cell death in the later reoxygenation phase / Scorziello, A., Pellegrini, C., Secondo, A., Sirabella, R., Formisano, L., Sibaud, L., Amoroso, S., Canzoniero, L., Annunziato, L., DI RENZO, G.M.L.. - In: JOURNAL OF NEUROSCIENCE RESEARCH. - ISSN 0360-4012. - STAMPA. - 76:6(2004), pp. 812-821. [10.1002/jnr.20096]
Abstract:
The present study investigated the temporal relationship between neuronal nitric oxide synthase (nNOS) activity and expression and the development of neuronal damage occurring during anoxia and anoxia followed by reoxygenation. For this purpose, cerebellar granule cells were exposed to 2 hr of oxyge...n and glucose deprivation (OGD) and 24 hr of reoxygenation. To clarify the consequences of nNOS activity inhibition on neuronal survival, cerebellar granule cells were exposed to OGD, both in the absence of extracellular Na(+) ([Na(+)](e)), a condition that by reducing intracellular Ca(2+) ([Ca(2+)](I)) prevents Ca(2+)-dependent nNOS activation, and in the presence of selective and nonselective nNOS inhibitors, such as N(omega)-L-allyl-L-arginine (L-ALA), N(omega)-propyl-L-arginine (NPLA), and L-nitro-arginine-methyl-ester (L-NAME), respectively. The results demonstrated that the removal of [Na(+)](e) hampered the [Ca(2+)](i) increase and decreased expression and activity of nNOS. Similarly, the increase of free radical production present in cerebellar neurons, exposed previously to OGD and OGD/reoxygenation, was abolished completely in the absence of [Na(+)](e). Furthermore, the absence of [Na(+)](e) in cerebellar neurons exposed to 2 hr of OGD led to the improvement of mitochondrial activity and neuronal survival, both after the OGD phase and after 24 hr of reoxygenation. Finally, the exposure of cerebellar neurons to L-ALA (200 nM), and L-NAME (500 microM) was able to effectively reduce NO(*) production and caused an increase in mitochondrial oxidative activity and an improvement of neuronal survival not only during OGD, but also during reoxygenation. Similar results during OGD were obtained also with NPLA (5 nM), another selective nNOS inhibitor. These data suggest that the activation of nNOS is highly accountable for the neuronal damage occurring during the OGD and reoxygenation phases.
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Effects of HIV-1 Tat protein on ion secretion and on cell proliferation in human intestinal epithelial cells
Anno: 2003
Rivista: GASTROENTEROLOGY
Autori/autrici: BERNI CANANI, Roberto; Cirillo, P; Mallardo, G; Buccigrossi, V; Secondo, Agnese; Annunziato, L; Bruzzese, E; Albano, F; Selvaggi, F; Guarino, Alfredo
Classificazione IRIS: 1.1 Articolo in rivista
Scheda completa IRIS: https://iris.univpm.it/handle/11566/337764
Citazioni:
Effects of HIV-1 Tat protein on ion secretion and on cell proliferation in human intestinal epithelial cells / BERNI CANANI, Roberto; Cirillo, P; Mallardo, G; Buccigrossi, V; Secondo, Agnese; Annunziato, L; Bruzzese, E; Albano, F; Selvaggi, F; Guarino, Alfredo. - In: GASTROENTEROLOGY. - ISSN 0016-5085. - 124:(2003), pp. 368-376.

Involvement of PI3-K, mitogen-activated protein kinase and PKB in the upregulation of the expression of nNOSalpha and nNOSbeta splicing variants induced by PRL-receptor actvation in GH3 cells
Anno: 2003
Rivista: JOURNAL OF NEUROCHEMISTRY
Autori/autrici: Secondo, Agnese; Sirabella, Rossana; Formisano, L; D'Alessio, A; Castaldo, P; Amoroso, S; Ingleton, P; DI RENZO, GIANFRANCO MARIA LUIGI; Annunziato, L.
Classificazione IRIS: 1.1 Articolo in rivista
Scheda completa IRIS: https://iris.univpm.it/handle/11566/337709
Citazioni:
Involvement of PI3-K, mitogen-activated protein kinase and PKB in the upregulation of the expression of nNOSalpha and nNOSbeta splicing variants induced by PRL-receptor actvation in GH3 cells / Secondo, A., Sirabella, R., Formisano, L., D'Alessio, A., Castaldo, P., Amoroso, S., Ingleton, P., DI RENZO, G.M.L., Annunziato, L.. - In: JOURNAL OF NEUROCHEMISTRY. - ISSN 0022-3042. - 6:(2003), pp. 1367-1377.

Involvement of PI3'-K, mitogen-activated protein kinase and protein kinase B in the up-regulation of the expression of nNOSalpha and nNOSbeta splicing variants induced by PRL-receptor activation in GH3 cells
Anno: 2003
Rivista: JOURNAL OF NEUROCHEMISTRY
Autori/autrici: Secondo, A.; Sirabella, R.; Formisano, L.; D'Alessio, A.; Castaldo, Pasqualina; Amoroso, Salvatore; Ingleton, P.; DI RENZO, G.; Annunziato, L.
Classificazione IRIS: 1.1 Articolo in rivista
Scheda completa IRIS: https://iris.univpm.it/handle/11566/53207
Citazioni:
Involvement of PI3'-K, mitogen-activated protein kinase and protein kinase B in the up-regulation of the expression of nNOSalpha and nNOSbeta splicing variants induced by PRL-receptor activation in GH3 cells / Secondo, A., Sirabella, R., Formisano, L., D'Alessio, A., Castaldo, P., Amoroso, S., Ingleton, P., DI RENZO, G., Annunziato, L.. - In: JOURNAL OF NEUROCHEMISTRY. - ISSN 0022-3042. - 84:(2003), pp. 1367-1377.

Apoptosis induced in neuronal cells by oxidative stress: role played by caspases and intracellular calcium ions
Anno: 2003
Rivista: TOXICOLOGY LETTERS
Autori/autrici: Annunziato, L.; Amoroso, Salvatore; Pannaccione, A.; Cataldi, M.; Pignataro, G.; D'Alessio, A.; Sirabella, R.; Secondo, A.; Sibaud, L.; DI RENZO, G.
Classificazione IRIS: 1.1 Articolo in rivista
Scheda completa IRIS: https://iris.univpm.it/handle/11566/26342
Citazioni:
Apoptosis induced in neuronal cells by oxidative stress: role played by caspases and intracellular calcium ions / Annunziato, L., Amoroso, S., Pannaccione, A., Cataldi, M., Pignataro, G., D'Alessio, A., Sirabella, R., Secondo, A., Sibaud, L., DI RENZO, G.. - In: TOXICOLOGY LETTERS. - ISSN 0378-4274. - 139:(2003), pp. 125-133.

Effects of HIV 1 Tat protein on ion secretion and on cell proliferation in human intestinal epithelial cells
Anno: 2003
Rivista: GASTROENTEROLOGY
Autori/autrici: BERNI CANANI, Roberto; Cirillo, P; Mallardo, G; Buccigrossi, V; Secondo, Agnese; Annunziato, Lucio; Bruzzese, Eugenia; Albano, F; Selvaggi, F; Guarino, Alfredo
Classificazione IRIS: 1.1 Articolo in rivista
Scheda completa IRIS: https://iris.univpm.it/handle/11566/337735
Citazioni:
Effects of HIV 1 Tat protein on ion secretion and on cell proliferation in human intestinal epithelial cells / BERNI CANANI, R., Cirillo, P., Mallardo, G., Buccigrossi, V., Secondo, A., Annunziato, L., Bruzzese, E., Albano, F., Selvaggi, F., Guarino, A.. - In: GASTROENTEROLOGY. - ISSN 0016-5085. - STAMPA. - 124:(2003), pp. 368-376.
Abstract:
BACKGROUND & AIMS: Severe diarrhea and enteropathy of unknown origin are frequent in patients infected with human immunodeficiency type 1 virus (HIV-1). The HIV-1 transactivating factor protein (Tat) is a key factor in the pathogenesis of acquired immunodeficiency syndrome. We investigated w...hether Tat could directly induce ion secretion and cell damage in enterocytes. METHODS: Electrical parameters (ion transport studies) were measured in Caco-2 cell monolayers and in human colonic mucosa specimens mounted in Ussing chambers. The effect of Tat on intestinal mucosa integrity was determined by monitoring the transepithelial electrical resistance of Caco-2 cell monolayers. (3)H-thymidine incorporation and cell count were used to evaluate the effect of Tat on cell growth. Intracellular calcium concentrations were measured at the single-cell level using microfluorometry technique. RESULTS: Tat protein induced ion secretion in Caco-2 cells and in human colonic mucosa similar to that induced by bacterial enterotoxins. It also significantly prevented enterocyte proliferation. In both instances, the effect of Tat was maximum at concentrations within the range detected in the sera of HIV-1-infected patients. Anti-Tat antibodies inhibited both effects. Ion secretion and the antiproliferative effects were mediated by L-type Ca(2+) channels. An increase in intracellular calcium concentration in Caco-2 cells was found after addition of Tat. CONCLUSIONS: These results indicate that Tat may be involved in HIV-1-related intestinal disease through direct interaction with enterocytes.
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Effects of HIV-1 Tat protein on ion secretion and on cell proliferation in human intestinal epithelial cells
Anno: 2003
Rivista: GASTROENTEROLOGY
Autori/autrici: Berni Canani, R; Cirillo, P; Mallardo, G; Buccigrossi, V; Secondo, A; Annunziato, L; Bruzzese, E; Albano, F; Selvaggi, F; Guarino, A
Lingua: ENG
Classificazione IRIS: 1.1 Articolo in rivista
Scheda completa IRIS: https://iris.univpm.it/handle/11566/337682
Citazioni:
Effects of HIV-1 Tat protein on ion secretion and on cell proliferation in human intestinal epithelial cells / Berni Canani, R., Cirillo, P., Mallardo, G., Buccigrossi, V., Secondo, A., Annunziato, L., Bruzzese, E., Albano, F., Selvaggi, F., Guarino, A.. - In: GASTROENTEROLOGY. - ISSN 0016-5085. - STAMPA. - 124:2(2003), pp. 368-376. [10.1053/gast.2003.50056]
Abstract:
BACKGROUND & AIMS: Severe diarrhea and enteropathy of unknown origin are frequent in patients infected with human immunodeficiency type 1 virus (HIV-1). The HIV-1 transactivating factor protein (Tat) is a key factor in the pathogenesis of acquired immunodeficiency syndrome. We investigated wheth...er Tat could directly induce ion secretion and cell damage in enterocytes. METHODS: Electrical parameters (ion transport studies) were measured in Caco-2 cell monolayers and in human colonic mucosa specimens mounted in Ussing chambers. The effect of Tat on intestinal mucosa integrity was determined by monitoring the transepithelial electrical resistance of Caco-2 cell monolayers. (3)H-thymidine incorporation and cell count were used to evaluate the effect of Tat on cell growth. Intracellular calcium concentrations were measured at the single-cell level using microfluorometry technique. RESULTS: Tat protein induced ion secretion in Caco-2 cells and in human colonic mucosa similar to that induced by bacterial enterotoxins. It also significantly prevented enterocyte proliferation. In both instances, the effect of Tat was maximum at concentrations within the range detected in the sera of HIV-1-infected patients. Anti-Tat antibodies inhibited both effects. Ion secretion and the antiproliferative effects were mediated by L-type Ca(2+) channels. An increase in intracellular calcium concentration in Caco-2 cells was found after addition of Tat. CONCLUSIONS: These results indicate that Tat may be involved in HIV-1-related intestinal disease through direct interaction with enterocytes.
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Effects of HIV-1 Tat protein on ion secretion and on cell proliferation in Human intestinal epithelial cells
Anno: 2003
Rivista: GASTROENTEROLOGY
Autori/autrici: BERNI CANANI, Roberto; Cirillo, P; Mallardo, G; Buccigrossi, V; Secondo, Agnese; Annunziato, L; Bruzzese, Eugenia; Albano, F; Selvaggi, F; Guarino, Alfredo
Classificazione IRIS: 1.1 Articolo in rivista
Scheda completa IRIS: https://iris.univpm.it/handle/11566/337721
Citazioni:
Effects of HIV-1 Tat protein on ion secretion and on cell proliferation in Human intestinal epithelial cells / BERNI CANANI, R., Cirillo, P., Mallardo, G., Buccigrossi, V., Secondo, A., Annunziato, L., Bruzzese, E., Albano, F., Selvaggi, F., Guarino, A.. - In: GASTROENTEROLOGY. - ISSN 0016-5085. - STAMPA. - 124:2(2003), pp. 368-376.
Abstract:
AIMS: Severe diarrhea and enteropathy of unknown origin are frequent in patients infected with human immunodeficiency type 1 virus (HIV-1). The HIV-1 transactivating factor protein (Tat) is a key factor in the pathogenesis of acquired immunodeficiency syndrome. We investigated whether Tat could dire...ctly induce ion secretion and cell damage in enterocytes. METHODS: Electrical parameters (ion transport studies) were measured in Caco-2 cell monolayers and in human colonic mucosa specimens mounted in Ussing chambers. The effect of Tat on intestinal mucosa integrity was determined by monitoring the transepithelial electrical resistance of Caco-2 cell monolayers. (3)H-thymidine incorporation and cell count were used to evaluate the effect of Tat on cell growth. Intracellular calcium concentrations were measured at the single-cell level using microfluorometry technique. RESULTS: Tat protein induced ion secretion in Caco-2 cells and in human colonic mucosa similar to that induced by bacterial enterotoxins. It also significantly prevented enterocyte proliferation. In both instances, the effect of Tat was maximum at concentrations within the range detected in the sera of HIV-1-infected patients. Anti-Tat antibodies inhibited both effects. Ion secretion and the antiproliferative effects were mediated by L-type Ca(2+) channels. An increase in intracellular calcium concentration in Caco-2 cells was found after addition of Tat. CONCLUSIONS: These results indicate that Tat may be involved
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Na+/Ca2+ exchanger in Na+ efflux-Ca2+ influx mode of operation exerts a neuroprotective role in cellular models of in vitro anoxia and in vivo cerebral ischemia
Anno: 2002
Rivista: ANNALS OF THE NEW YORK ACADEMY OF SCIENCES
Autori/autrici: Tortiglione, A; Pignataro, G; Minale, M; Secondo, A; Scorziello, A; DI RENZO, Gf; Amoroso, Salvatore; Caliendo, G; Santagada, V; Annunziato, L.
Classificazione IRIS: 1.1 Articolo in rivista
Scheda completa IRIS: https://iris.univpm.it/handle/11566/26349
Citazioni:
Na+/Ca2+ exchanger in Na+ efflux-Ca2+ influx mode of operation exerts a neuroprotective role in cellular models of in vitro anoxia and in vivo cerebral ischemia / Tortiglione, A; Pignataro, G; Minale, M; Secondo, A; Scorziello, A; DI RENZO, Gf; Amoroso, Salvatore; Caliendo, G; Santagada, V; Annunziato, L.. - In: ANNALS OF THE NEW YORK ACADEMY OF SCIENCES. - ISSN 0077-8923. - 976:(2002), pp. 408-412.

Modulation of ion channels by reactive oxygen and nitrogen species: a pathophysiological role in brain aging?
Anno: 2002
Rivista: NEUROBIOLOGY OF AGING
Autori/autrici: Annunziato, L; Pannaccione, A; Cataldi, M; Secondo, A; Castaldo, Pasqualina; DI RENZO, G; Taglialatela, M.
Classificazione IRIS: 1.1 Articolo in rivista
Scheda completa IRIS: https://iris.univpm.it/handle/11566/37238
Citazioni:
Modulation of ion channels by reactive oxygen and nitrogen species: a pathophysiological role in brain aging? / Annunziato, L., Pannaccione, A., Cataldi, M., Secondo, A., Castaldo, P., DI RENZO, G., Taglialatela, M.. - In: NEUROBIOLOGY OF AGING. - ISSN 0197-4580. - 23:(2002), pp. 819-834.

Inhibition of depolarization-induced [3H]noradrenaline release from SH-SY5Y human neuroblastoma cells by some second-generation H(1) receptor antagonists through blockade of store-operated Ca(2+) channels (SOCs).
Anno: 2001
Rivista: BIOCHEMICAL PHARMACOLOGY
Autori/autrici: Taglialatela, M.; Secondo, A.; Fresi, A.; Rosati, B.; Pannaccione, A.; Castaldo, Pasqualina; Giorgio, G.; Wanke, E.; Annunziato, L.
Classificazione IRIS: 1.1 Articolo in rivista
Scheda completa IRIS: https://iris.univpm.it/handle/11566/54913
Citazioni:
Inhibition of depolarization-induced [3H]noradrenaline release from SH-SY5Y human neuroblastoma cells by some second-generation H(1) receptor antagonists through blockade of store-operated Ca(2+) channels (SOCs) / Taglialatela, M., Secondo, A., Fresi, A., Rosati, B., Pannaccione, A., Castaldo, P., Giorgio, G., Wanke, E., Annunziato, L.. - In: BIOCHEMICAL PHARMACOLOGY. - ISSN 0006-2952. - 62:(2001), pp. 1229-1238.

'Janus face' of nitric oxide action on plasma membrane and intracellular ionic channels
Anno: 2001
Rivista: ARCHIVES OF GERONTOLOGY AND GERIATRICS
Autori/autrici: Taglialatela, M; Pannaccione, A; Cataldi, M; Castaldo, Pasqualina; Secondo, A; Iossa, S; DI RENZO, Gf; Annunziato, L.
Classificazione IRIS: 1.1 Articolo in rivista
Scheda completa IRIS: https://iris.univpm.it/handle/11566/37239
Citazioni:
'Janus face' of nitric oxide action on plasma membrane and intracellular ionic channels / Taglialatela, M., Pannaccione, A., Cataldi, M., Castaldo, P., Secondo, A., Iossa, S., DI RENZO, G.f., Annunziato, L.. - In: ARCHIVES OF GERONTOLOGY AND GERIATRICS. - ISSN 0167-4943. - 33:(2001), pp. 379-394.

Histamine induces exocytosis and IL-6 production from human lung macrophages through interaction with H1 receptors
Anno: 2001
Rivista: JOURNAL OF IMMUNOLOGY
Autori/autrici: Triggiani, M; Gentile, M; Secondo, Agnese; Granata, F; Oriente, A; Taglialatela, Maurizio; Annunziato, Lucio; Marone, G.
Lingua: ENG
Classificazione IRIS: 1.1 Articolo in rivista
Scheda completa IRIS: https://iris.univpm.it/handle/11566/337671
Citazioni:
Histamine induces exocytosis and IL-6 production from human lung macrophages through interaction with H1 receptors / Triggiani, M., Gentile, M., Secondo, A., Granata, F., Oriente, A., Taglialatela, M., Annunziato, L., Marone, G.. - In: JOURNAL OF IMMUNOLOGY. - ISSN 0022-1767. - STAMPA. - 166:6(2001), pp. 4083-4091.
Abstract:
Increasing evidence suggests that a continuous release of histamine from mast cells occurs in the airways of asthmatic patients and that histamine may modulate functions of other inflammatory cells such as macrophages. In the present study histamine (10(-9)-10(-6) M) increased in a concentration-dep...endent fashion the basal release of beta-glucuronidase (EC(50) = 8.2 +/- 3.5 x 10(-9) M) and IL-6 (EC(50) = 9.3 +/- 2.9 x 10(-8) M) from human lung macrophages. Enhancement of beta-glucuronidase release induced by histamine was evident after 30 min and peaked at 90 min, whereas that of IL-6 required 2-6 h of incubation. These effects were reproduced by the H(1) agonist (6-[2-(4-imidazolyl)ethylamino]-N-(4-trifluoromethylphenyl)heptane carboxamide but not by the H(2) agonist dimaprit. Furthermore, histamine induced a concentration-dependent increase of intracellular Ca(2+) concentrations ([Ca(2+)](i)) that followed three types of response, one characterized by a rapid increase, a second in which [Ca(2+)](i) displays a slow but progressive increase, and a third characterized by an oscillatory pattern. Histamine-induced beta-glucuronidase and IL-6 release and [Ca(2+)](i) elevation were inhibited by the selective H(1) antagonist fexofenadine (10(-7)-10(-4) M), but not by the H(2) antagonist ranitidine. Inhibition of histamine-induced beta-glucuronidase and IL-6 release by fexofenadine was concentration dependent and displayed the characteristics of a competitive antagonism (K(d) = 89 nM). These data demonstrate that histamine induces exocytosis and IL-6 production from human macrophages by activating H(1) receptor and by increasing [Ca(2+)](i) and they suggest that histamine may play a relevant role in the long-term sustainment of allergic inflammation in the airways.
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Pharmacological blockade of ERG K+ channels and Ca2+ influx through store-operated channels exerts opposite effects on intracellular Ca2+ oscillations in pituitary GH3 cells
Anno: 2000
Rivista: MOLECULAR PHARMACOLOGY
Autori/autrici: Secondo, Agnese; Taglialatela, Maurizio; Cataldi, Mauro; Giorgio, G.; Valore, M.; DI RENZO, GIANFRANCO MARIA LUIGI; Annunziato, L.
Classificazione IRIS: 1.1 Articolo in rivista
Scheda completa IRIS: https://iris.univpm.it/handle/11566/337688
Citazioni:
Pharmacological blockade of ERG K+ channels and Ca2+ influx through store-operated channels exerts opposite effects on intracellular Ca2+ oscillations in pituitary GH3 cells / Secondo, Agnese; Taglialatela, Maurizio; Cataldi, Mauro; Giorgio, G.; Valore, M.; DI RENZO, GIANFRANCO MARIA LUIGI; Annunziato, L.. - In: MOLECULAR PHARMACOLOGY. - ISSN 0026-895X. - 58:(2000), pp. 1115-1128.

pharmacological blockade of ERG K+ channels and Ca2+ influx through store-operated channels exerts opposite effects on intracellular Ca2+ oscillations in pituitary gh3 cells
Anno: 2000
Rivista: MOLECULAR PHARMACOLOGY
Autori/autrici: Secondo, Agnese; Taglialatela, M.; Cataldi, Mauro; Giorgio, G.; Valore, M.; DI RENZO, GIANFRANCO MARIA LUIGI; AND ANNUNZIATO, L.
Classificazione IRIS: 1.1 Articolo in rivista
Scheda completa IRIS: https://iris.univpm.it/handle/11566/337754
Citazioni:
pharmacological blockade of ERG K+ channels and Ca2+ influx through store-operated channels exerts opposite effects on intracellular Ca2+ oscillations in pituitary gh3 cells / Secondo, Agnese; Taglialatela, M.; Cataldi, Mauro; Giorgio, G.; Valore, M.; DI RENZO, GIANFRANCO MARIA LUIGI; AND ANNUNZIATO, L.. - In: MOLECULAR PHARMACOLOGY. - ISSN 0026-895X. - 58:(2000), pp. 1115-1128.

Sodium nitroprusside prevents chemical hypoxya-induced cell death through iron ions stimulating the activity of the Na+-Ca2+ exchanger in C6 glioma cells.
Anno: 2000
Rivista: JOURNAL OF NEUROCHEMISTRY
Autori/autrici: Amoroso, Salvatore; Tortiglione, A.; Secondo, A.; Catalano, A.; Montagnani, S.; DI RENZO, G. F.; Annunziato, L.
Classificazione IRIS: 1.1 Articolo in rivista
Scheda completa IRIS: https://iris.univpm.it/handle/11566/26218
Citazioni:
Sodium nitroprusside prevents chemical hypoxya-induced cell death through iron ions stimulating the activity of the Na+-Ca2+ exchanger in C6 glioma cells / Amoroso, S., Tortiglione, A., Secondo, A., Catalano, A., Montagnani, S., DI RENZO, G.F., Annunziato, L.. - In: JOURNAL OF NEUROCHEMISTRY. - ISSN 0022-3042. - 74:(2000), pp. 1505-1513.

Pharmacological blockade of ERG K(+) channels and Ca(2+) influx through store-operated channels exerts opposite effects on intracellular Ca(2+) oscillations in pituitary GH(3) cells
Anno: 2000
Rivista: MOLECULAR PHARMACOLOGY
Autori/autrici: Triggiani, M; Gentile, M; Secondo, Agnese; Granata, F; Oriente, A; Taglialatela, M; Annunziato, L; Marone, G.
Classificazione IRIS: 1.1 Articolo in rivista
Scheda completa IRIS: https://iris.univpm.it/handle/11566/337702
Citazioni:
Pharmacological blockade of ERG K(+) channels and Ca(2+) influx through store-operated channels exerts opposite effects on intracellular Ca(2+) oscillations in pituitary GH(3) cells / Triggiani, M., Gentile, M., Secondo, A., Granata, F., Oriente, A., Taglialatela, M., Annunziato, L., Marone, G.. - In: MOLECULAR PHARMACOLOGY. - ISSN 0026-895X. - 58:(2000), pp. 1115-1128.

Pharmacological blockade of ERG K(+) channels and Ca(2+) influx through store-operated channels exerts opposite effects on intracellular Ca(2+) oscillations in pituitary GH(3) cells
Anno: 2000
Rivista: MOLECULAR PHARMACOLOGY
Autori/autrici: Secondo, Agnese; Taglialatela, Maurizio; Cataldi, Mauro; Giorgio, G; Valore, M; DI RENZO, GIANFRANCO MARIA LUIGI; Annunziato, Lucio
Lingua: ENG
Classificazione IRIS: 1.1 Articolo in rivista
Scheda completa IRIS: https://iris.univpm.it/handle/11566/337699
Citazioni:
Pharmacological blockade of ERG K(+) channels and Ca(2+) influx through store-operated channels exerts opposite effects on intracellular Ca(2+) oscillations in pituitary GH(3) cells / Secondo, A., Taglialatela, M., Cataldi, M., Giorgio, G., Valore, M., DI RENZO, G.M.L., Annunziato, L.. - In: MOLECULAR PHARMACOLOGY. - ISSN 0026-895X. - STAMPA. - 58:5(2000), pp. 1115-1128.
Abstract:
In the present study, the effects on intracellular calcium concentration ([Ca(2+)](i)) oscillations of the blockade of ether-a-go-go-related gene (ERG) K(+) channels and of Ca(2+) influx through store-operated channels (SOC) activated by [Ca(2+)](i) store depletion have been studied in GH(3) cells b...y means of a combination of single-cell fura-2 microfluorimetry and whole-cell mode of the patch-clamp technique. Nanomolar concentrations (1-30 nM) of the piperidinic second-generation antihistamines terfenadine and astemizole and of the class III antiarrhythmic methanesulfonanilide dofetilide, by blocking ERG K(+) channels, increased the frequency and the amplitude of [Ca(2+)](i) oscillations in resting oscillating GH(3) cells. These compounds also induced the appearance of an oscillatory pattern of [Ca(2+)](i) in a subpopulation of nonoscillating GH(3) cells. The effects of ERG K(+) channel blockade on [Ca(2+)](i) oscillations appeared to be due to the activation of L-type Ca(2+) channels, because they were prevented by 300 nM nimodipine. By contrast, the piperazinic second-generation antihistamine cetirizine (0.01-30 microM), which served as a negative control, failed to affect ERG K(+) channels and did not interfere with [Ca(2+)](i) oscillations in GH(3) cells. Interestingly, micromolar concentrations of terfenadine and astemizole (0.3-30 microM), but not of dofetilide (10-100 microM), produced an inhibition of the spontaneous oscillatory pattern of [Ca(2+)](i) changes. This effect was possibly related to an inhibition of SOC, because these compounds inhibited the increase of [Ca(2+)](i) achieved by extracellular calcium reintroduction after intracellular calcium store depletion with the sarcoplasmic or endoplasmic reticulum calcium ATPase pump inhibitor thapsigargin (10 microM) in an extracellular calcium-free medium. The same inhibitory effect on [Ca(2+)](i) oscillations and SOC was observed with the first-generation antihistamine hydroxyzine (1-30 microM), the more hydrophobic metabolic precursor of cetirizine. Collectively, the results of the present study obtained with compounds that interfere in a different concentration range with ERG K(+) channels or SOC suggest that 1) ERG K(+) channels play a relevant role in controlling the oscillatory pattern of [Ca(2+)](i) in resting GH(3) cells and 2) the inhibition of SOC might induce an opposite effect, i.e., an inhibition of [Ca(2+)](i) oscillations.
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Pharmacological blockade of ERG K(+) channels and Ca(2+) influx through store-operated channels exerts opposite effects on intracellular Ca(2+) oscillations in pituitary GH(3) cells
Anno: 2000
Rivista: MOLECULAR PHARMACOLOGY
Autori/autrici: Secondo, Agnese; Taglialatela, M; Cataldi, Mauro; Giorgio, G; Valore, M; DI RENZO, GIANFRANCO MARIA LUIGI; Annunziato, L.
Classificazione IRIS: 1.1 Articolo in rivista
Scheda completa IRIS: https://iris.univpm.it/handle/11566/337759
Citazioni:
Pharmacological blockade of ERG K(+) channels and Ca(2+) influx through store-operated channels exerts opposite effects on intracellular Ca(2+) oscillations in pituitary GH(3) cells / Secondo, A., Taglialatela, M., Cataldi, M., Giorgio, G., Valore, M., DI RENZO, G.M.L., Annunziato, L.. - In: MOLECULAR PHARMACOLOGY. - ISSN 0026-895X. - 58:(2000), pp. 1115-1128.

Sodium nitroprusside prevents chemical hypoxia-induced cell death through iron ions stimulating the activity of the Na+-Ca2+ exchanger in C6 glioma cells
Anno: 2000
Rivista: JOURNAL OF NEUROCHEMISTRY
Autori/autrici: Amoroso, S; Tortiglione, A; Secondo, Agnese; Catalano, A; Montagnani, Stefania; DI RENZO, GIANFRANCO MARIA LUIGI; Annunziato, Lucio
Lingua: ENG
Classificazione IRIS: 1.1 Articolo in rivista
Scheda completa IRIS: https://iris.univpm.it/handle/11566/337673
Citazioni:
Sodium nitroprusside prevents chemical hypoxia-induced cell death through iron ions stimulating the activity of the Na+-Ca2+ exchanger in C6 glioma cells / Amoroso, S., Tortiglione, A., Secondo, A., Catalano, A., Montagnani, S., DI RENZO, G.M.L., Annunziato, L.. - In: JOURNAL OF NEUROCHEMISTRY. - ISSN 0022-3042. - STAMPA. - 74:4(2000), pp. 1505-1513. [10.1046/j.1471-4159.2000.0741505.x]
Abstract:
In C6 glioma cells exposed to chemical hypoxia, an increase of extracellular lactate dehydrogenase (LDH) activity, cell death, and intracellular Ca2+ concentration ([Ca2+]i) occurred. Sodium nitroprusside (SNP), a nitric oxide donor and an iron-containing molecule, reduced chemical hypoxia-induced L...DH release and cell death. These effects were counteracted by bepridil and by 5-(N-4-chlorobenzyl)-2',4'-dimethylbenzamil (CB-DMB), two specific inhibitors of the Na+-Ca2+ exchanger. SNP also increased the activity of the Na+-Ca2+ exchanger as a Na+ efflux pathway, stimulated by Na+-free conditions and evaluated by monitoring [Ca2+]i in single cells. In addition, SNP produced a further increase of chemical hypoxia-elicited [Ca2+]i elevation, and this effect was blocked by bepridil. Chemical hypoxia-evoked cell death and LDH release were counteracted by the ferricyanide moiety of the SNP molecule, K3Fe(CN)6, and by ferric chloride (FeCl3), and this effect was counteracted by CB-DMB. In addition, the iron ion chelator deferoxamine reversed the protective effect exerted by SNP on cell injury. Collectively, these findings suggest that the protective effect of SNP on C6 glioma cells exposed to chemical hypoxia is due to the activation of the Na+-Ca2+ exchanger operating as a Na+ efflux-Ca2+ influx pathway induced by iron present in the SNP molecule.
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Involvement of phosphodiesterase-cGMP-PKG pathway in intracellular Ca2+ oscillations in pituitary GH3 cells
Anno: 1999
Rivista: BIOCHIMICA ET BIOPHYSICA ACTA
Autori/autrici: Cataldi, M; Secondo, A; D'Alessio, A; Sarnacchiaro, F; Colao, Am; Amoroso, Salvatore; DI RENZO, Gf; Annunziato, L.
Classificazione IRIS: 1.1 Articolo in rivista
Scheda completa IRIS: https://iris.univpm.it/handle/11566/26352
Citazioni:
Involvement of phosphodiesterase-cGMP-PKG pathway in intracellular Ca2+ oscillations in pituitary GH3 cells / Cataldi, M; Secondo, A; D'Alessio, A; Sarnacchiaro, F; Colao, Am; Amoroso, Salvatore; DI RENZO, Gf; Annunziato, L.. - In: BIOCHIMICA ET BIOPHYSICA ACTA. - ISSN 0006-3002. - 1449:(1999), pp. 186-193.

Effects of manidipine and nitrendipine enantiomers on the plateau phase of K+-induced intracellular Ca2+ increase in GH3 cells
Anno: 1999
Rivista: EUROPEAN JOURNAL OF PHARMACOLOGY
Autori/autrici: Cataldi, M; Taglialatela, M; Palagiano, F; Secondo, A; DE CAPRARIIS, P; Amoroso, Salvatore; DI RENZO, G; Annunziato, L.
Classificazione IRIS: 1.1 Articolo in rivista
Scheda completa IRIS: https://iris.univpm.it/handle/11566/26351
Citazioni:
Effects of manidipine and nitrendipine enantiomers on the plateau phase of K+-induced intracellular Ca2+ increase in GH3 cells / Cataldi, M; Taglialatela, M; Palagiano, F; Secondo, A; DE CAPRARIIS, P; Amoroso, Salvatore; DI RENZO, G; Annunziato, L.. - In: EUROPEAN JOURNAL OF PHARMACOLOGY. - ISSN 0014-2999. - 376:(1999), pp. 169-178.

Studies on maitotoxin-induced intracellular Ca(2+) elevation in chinese hamster ovary cells stably transfected with cDNAs encoding for L-type Ca(2+) channel subunits
Anno: 1999
Rivista: THE JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
Autori/autrici: Cataldi, Mauro; Secondo, Agnese; D'Alessio, A; Taglialatela, Maurizio; Hofmann, F; Klugbauer, N; DI RENZO, GIANFRANCO MARIA LUIGI; Annunziato, Lucio
Lingua: ENG
Classificazione IRIS: 1.1 Articolo in rivista
Scheda completa IRIS: https://iris.univpm.it/handle/11566/337733
Citazioni:
Studies on maitotoxin-induced intracellular Ca(2+) elevation in chinese hamster ovary cells stably transfected with cDNAs encoding for L-type Ca(2+) channel subunits / Cataldi, M., Secondo, A., D'Alessio, A., Taglialatela, M., Hofmann, F., Klugbauer, N., DI RENZO, G.M.L., Annunziato, L.. - In: THE JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS. - ISSN 0022-3565. - STAMPA. - 290:2(1999), pp. 725-730.
Abstract:
The aim of the present study was to characterize the role played by different L-type Ca(2+) channel subunits in [Ca(2+)](i) increase induced by maitotoxin (MTX). In the presence of 5 mM extracellular K(+), MTX (0.01-0.5 ng/ml) induced a significant concentration-dependent increase in Fura-2-monitore...d [Ca(2+)](i) in single Chinese hamster ovary (CHO) cells expressing the alpha(1c) (CHOCalpha9 cells) or the alpha(1c)beta(3)alpha(2)delta (CHOCalpha9beta3alpha2/delta4 cells) subunits of voltage-gated Ca(2+) channels (VGCCs), whereas the effect was much reduced in wild-type CHO cells lacking VGCCs. In addition, MTX effect on CHOCalpha9, CHOCalpha9beta3alpha2/delta4, and GH(3) cells (0.01-0.1 ng/ml) was inhibited by the selective L-type Ca(2+) channel entry-blocker nimodipine (10 microM); a nimodipine-insensitive component was still present, particularly at high (>1 ng/ml) toxin concentrations. In CHOCalpha9beta3alpha2/delta4 cells, depolarizing concentrations of extracellular K(+) (55 mM) reinforced the [Ca(2+)](i) increase induced by MTX (0.1 ng/ml), and this effect was prevented by nimodipine (10 microM). Finally, patch-clamp experiments in CHOCalpha9beta3alpha2/delta4 cells showed that low MTX concentrations (0.03 ng/ml) induced the occurrence of an inward current at -60 mV, which was completely prevented by Cd(2+) (100 microM) and by nimodipine (10 microM), whereas the same dihydropyridine concentration (10 microM) failed to prevent the electrophysiological effects of a higher toxin concentration (3 ng/ml). In conclusion, the results of the present study showed that MTX-induced [Ca(2+)](i) elevation involves two components: 1) an action on L-type VGCCs at the pore-forming alpha(1c) subunit level, which is responsible for the greatest rise of [Ca(2+)](i); and 2) a VGCC-independent mechanism that is present both in excitable and in nonexcitable cells and is responsible for a lower elevation of [Ca(2+)](i).
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