Neuroprotective properties of nitric oxide and S-nitrosoglutathione.
Oxidative stress and apoptosis may play an important role in the neurodegeneration. The present paper outlines antioxidative and antiapototic mechanisms of nitric oxide and S-nitrosothiols, which could mediate neuroprotection. Nitric oxide generated by nitric oxide synthase or released from an endogenous S-nitrosothiol, S-nitrosoglutathione may up-regulate antioxidative thioredoxin system and antiapototic Bcl-2 protein through a cGMP-dependent mechanism. Moreover, nitric oxide radicals have been shown to have direct antioxidant effect through their reaction with free radicals and iron-oxygen complexes. In addition to serving as a stabilizer and carrier of nitric oxide, S-nitrosoglutathione may have protective effect through transnitrosylation reactions. Based on these new findings, a hypothesis arises that the homeostasis of nitric oxide, S-nitrosothiols, glutathione, and thioredoxin systems is important for protection against oxidative stress, apoptosis, and related neurodegenerative disorders.
Institute of Biomedicine, Pharmacology, Biomedicum Helsinki, P.O. Box 63, University of Helsinki 00014, Helsinki, Finland. pekka.rauhala@helsinki.fi
Pekka
P
Rauhala
Tsugunobu
T
Andoh
Chuang C
CC
Chiueh
D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D006152:Cyclic GMP / Q000494:pharmacology; D006801:Humans; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009569:Nitric Oxide / Q000494:pharmacology*; D018384:Oxidative Stress; D026422:S-Nitrosoglutathione / Q000494:pharmacology*
D000975:Antioxidants; D018696:Neuroprotective Agents; D009569:Nitric Oxide; D026422:S-Nitrosoglutathione; D006152:Cyclic GMP