Sodium nitroprusside prevents chemical hypoxia-induced cell death through iron ions stimulating the activity of the Na+-Ca2+ exchanger in C6 glioma cells

Salvatore Amoroso, Anna Tortiglione, Agnese Secondo, Annalisa Catalano, Stefania Montagnani, Gianfranco Di Renzo, Lucio Annunziato

Research output: Contribution to journalArticlepeer-review

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 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.

Original languageEnglish
Pages (from-to)1505-1513
Number of pages9
JournalJournal of Neurochemistry
Volume74
Issue number4
DOIs
Publication statusPublished - 2000

Keywords

  • C6 glioma
  • Cell survival
  • Chemical hypoxia
  • Iron
  • Na-Ca exchanger
  • Sodium nitroprusside

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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