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

We found that several nitric oxide donors had similar potency in killing ma ture and immature forms of oligodendrocytes (OLs), Because of the possibili ty of interaction of nitric oxide with intracellular thiols, we tested the effect of the nitrosonium ion donor S-nitrosylglutathione (SNOG) in OL cult ures in the setting of cystine deprivation, which has been shown to cause i ntracellular glutathione depletion. Surprisingly, the presence of 200 mu M SNOG completely protected OLs against the toxicity of cystine depletion. Th is protection appeared to be due to nitric oxide, because it could be block ed by hemoglobin and potentiated by inclusion of superoxide dismutase, We t ested the effect of three additional NO. donors and found that protection w as not seen with diethylamine NONOate, a donor with a half-life measured in minutes, but was seen with dipropylenetriamine NONOate and diethylaminetri amine NONOate, donors with half-lives measured in hours. This need for dono rs with longer half-lives for the protective effect suggested that NO. was required when intracellular thiol concentrations were falling, a process ev olving over hours in medium depleted of cystine. These studies suggest a no vel protective role for nitric oxide in oxidative stress injury and raise t he possibility that intracerebral nitric oxide production might be a mechan ism of defense against oxidative stress injury in OLs.