Hydrogen sulfide protects neurons from oxidative stress.
Hydrogen sulfide (H2S), which is a well-known toxic gas, is found in relatively high concentrations in the brain. Although a neuromodulatory role of H2S has been demonstrated, little is known of its other biological functions. Here we show that H2S protects primary cultures of neurons from death in a well-studied model of oxidative stress caused by glutamate, a process called oxidative glutamate toxicity--or oxytosis. We found that H2S increases the glutathione levels, which normally decrease during the cell death cascade, by enhancing the activity of gamma-glutamylcysteine synthetase and up-regulating cystine transport. Cystine (cysteine) is the rate-limiting substrate of glutathione synthesis. These observations reveal that H2S protects neurons from oxytosis by increasing the production of the antioxidant glutathione.
Kimura
Yuka
Y
National Institute of Neuroscience, Kodaira, Tokyo, Japan.
Kimura
Hideo
H
D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002540:Cerebral Cortex / Q000166:cytology; D003545:Cysteine / Q000378:metabolism; D003553:Cystine / Q000378:metabolism; D004151:Dipeptides / Q000378:metabolism; D004790:Enzyme Induction / Q000187:drug effects; D005721:Glutamate-Cysteine Ligase / Q000235:genetics / Q000378:metabolism; D005978:Glutathione / Q000096:biosynthesis*; D006862:Hydrogen Sulfide / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley
D004151:Dipeptides; D018696:Neuroprotective Agents; D012333:RNA, Messenger; C030954:gamma-glutamylcystine; D003553:Cystine; D005721:Glutamate-Cysteine Ligase; D005978:Glutathione; D003545:Cysteine; D006862:Hydrogen Sulfide