Intracellular redox state determines whether nitric oxide is toxic or protective to rat oligodendrocytes in culture

Paul A. Rosenberg, Ya Li, Sanjida Ali, Nedret Altiok, Stephen A. Back, Joseph J. Volpe

Research output: Contribution to journalArticlepeer-review

78 Scopus citations


We found that several nitric oxide donors had similar potency in killing mature and immature forms of oligodendrocytes (OLs). Because of the possibility of interaction of nitric oxide with intracellular thiols, we tested the effect of the nitrosonium ion donor S-nitrosylglutathione (SNOG) in OL cultures in the setting of cystine deprivation, which has been shown to cause intracellular glutathione depletion. Surprisingly, the presence of 200 μM SNOG completely protected OLs against the toxicity of cystine depletion. This protection appeared to be due to nitric oxide, because it could be blocked by hemoglobin and potentiated by inclusion of superoxide dismutase. We tested the effect of three additional NO* donors and found that protection was not seen with diethylamine NONOate, a donor with a half-life measured in minutes, but was seen with dipropylenetriamine NONOate and diethylaminetriamine NONOate, donors with half-lives measured in hours. This need for donors with longer half-lives for the protective effect suggested that NO* was required when intracellular thiol concentrations were falling, a process evolving over hours in medium depleted of cystine. These studies suggest a novel protective role for nitric oxide in oxidative stress injury and raise the possibility that intracerebral nitric oxide production might be a mechanism of defense against oxidative stress injury in OLs.

Original languageEnglish (US)
Pages (from-to)476-484
Number of pages9
JournalJournal of neurochemistry
Issue number2
StatePublished - 1999
Externally publishedYes


  • Apoptosis
  • Death
  • Glutathione
  • Iron
  • Oxidation
  • Signal transduction

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience


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