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Sodium Nitroprusside Prevents Chemical Hypoxia‐Induced Cell Death Through Iron Ions Stimulating the Activity of the Na + ‐Ca 2+ Exchanger in C6 Glioma Cells
Author(s) -
Amoroso Salvatore,
Tortiglione Anna,
Secondo Agnese,
Catalano Annalisa,
Montagnani Stefania,
Di Renzo Gianfranco,
Annunziato Lucio
Publication year - 2000
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.2000.0741505.x
Subject(s) - sodium nitroprusside , chemistry , deferoxamine , bepridil , nitric oxide , programmed cell death , lactate dehydrogenase , biochemistry , apoptosis , calcium , enzyme , verapamil , organic chemistry
In C6 glioma cells exposed to chemical hypoxia, anincrease of extracellular lactate dehydrogenase (LDH) activity, cell death,and intracellular Ca 2+ concentration([Ca 2+ ] i ) occurred. Sodium nitroprusside (SNP), a nitricoxide donor and an iron‐containing molecule, reduced chemical hypoxia‐inducedLDH release and cell death. These effects were counteracted by bepridil and by5‐( N ‐4‐chlorobenzyl)‐2′,4′‐dimethylbenzamil (CB‐DMB), twospecific inhibitors of the Na + ‐Ca 2+ exchanger. SNP alsoincreased the activity of the Na + ‐Ca 2+ exchanger as aNa + efflux pathway, stimulated by Na + ‐free conditionsand evaluated by monitoring [Ca 2+ ] i in single cells. Inaddition, SNP produced a further increase of chemical hypoxia‐elicited[Ca 2+ ] i elevation, and this effect was blocked bybepridil. Chemical hypoxiaevoked cell death and LDH release were counteractedby the ferricyanide moiety of the SNP molecule,K 3 Fe(CN) 6 , and by ferric chloride (FeCl 3 ),and this effect was counteracted by CB‐DMB. In addition, the iron ion chelatordeferoxamine reversed the protective effect exerted by SNP on cell injury.Collectively, these findings suggest that the protective effect of SNP on C6glioma cells exposed to chemical hypoxia is due to the activation of theNa + ‐Ca 2+ exchanger operating as a Na + efflux‐Ca 2+ influx pathway induced by iron present in the SNP molecule.