TY - JOUR
T1 - Sodium nitroprusside prevents chemical hypoxia-induced cell death through iron ions stimulating the activity of the Na+-Ca2+ exchanger in C6 glioma cells
AU - Amoroso, Salvatore
AU - Tortiglione, Anna
AU - Secondo, Agnese
AU - Catalano, Annalisa
AU - Montagnani, Stefania
AU - Di Renzo, Gianfranco
AU - Annunziato, Lucio
PY - 2000
Y1 - 2000
N2 - 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 LDH release and cell death. These effects were counteracted by bepridil and by 5-(N-4-chlorobenzyl)-2',4'- dimethylbenzamil (CBDMB), 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.
AB - 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 LDH release and cell death. These effects were counteracted by bepridil and by 5-(N-4-chlorobenzyl)-2',4'- dimethylbenzamil (CBDMB), 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.
KW - C6 glioma
KW - Cell survival
KW - Chemical hypoxia
KW - Iron
KW - Na-Ca exchanger
KW - Sodium nitroprusside
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U2 - 10.1046/j.1471-4159.2000.0741505.x
DO - 10.1046/j.1471-4159.2000.0741505.x
M3 - Article
C2 - 10737607
AN - SCOPUS:0034071271
VL - 74
SP - 1505
EP - 1513
JO - Journal of Neurochemistry
JF - Journal of Neurochemistry
SN - 0022-3042
IS - 4
ER -