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.
Rauhala
Pekka
P
Institute of Biomedicine, Pharmacology, Biomedicum Helsinki, P.O. Box 63, University of Helsinki 00014, Helsinki, Finland. pekka.rauhala@helsinki.fi
Andoh
Tsugunobu
T
Chiueh
Chuang C
CC
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