The novel neuromodulator hydrogen sulfide: an endogenous peroxynitrite 'scavenger'?
Hydrogen sulfide (H2S) is a well-known cytotoxic gas. Recently it has been shown to stimulate N-methyl-D-aspartate (NMDA) receptors to enhance long-term potentiation suggesting a novel neuromodulatory role in vivo. Endogenous levels of H2S in the brain are reported to range between 10 and 160 microm. Considerably lower H2S levels are reported in the brains of Alzheimer's disease (AD) patients, where levels of brain protein nitration (probably mediated by peroxynitrite) are markedly increased. Activation of NMDA receptors leads to intracellular tyrosine nitration by peroxynitrite. Because H2S and peroxynitrite are important mediators in brain function and disease, we investigated the effects of the H2S 'donor', sodium hydrogen sulfide (NaSH) on peroxynitrite-mediated damage to biomolecules and to cultured human SH-SY5Y cells. H2S significantly inhibited peroxynitrite-mediated tyrosine nitration and inactivation of alpha1-antiproteinase to a similar extent to reduced glutathione at each concentration tested (30-250 microm). H2S also inhibited peroxynitrite-induced cytotoxicity, intracellular protein nitration and protein oxidation in human neuroblastoma SH-SY5Y cells. These data suggest that H2S has the potential to act as an inhibitor of peroxynitrite-mediated processes in vivo and that the potential antioxidant action of H2S deserves further study, given that extracellular GSH levels in the brain are very low.
Whiteman
Matthew
M
Department of Biochemistry, Faculty of Medicine, National University of Singapore, Republic of Singapore. bchwml@nus.edu.sg
Armstrong
Jeffrey S
JS
Chu
Siew Hwa
SH
Jia-Ling
Siau
S
Wong
Boon-Seng
BS
Cheung
Nam Sang
NS
Halliwell
Barry
B
Moore
Philip K
PK
D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D016166:Free Radical Scavengers / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D006862:Hydrogen Sulfide / Q000737:chemistry / Q000378:metabolism*; D009447:Neuroblastoma; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D018377:Neurotransmitter Agents / Q000737:chemistry / Q000378:metabolism*; D030421:Peroxynitrous Acid / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D013440:Sulfides / Q000378:metabolism / Q000494:pharmacology; D014443:Tyrosine / Q000737:chemistry
D016166:Free Radical Scavengers; D018377:Neurotransmitter Agents; D013440:Sulfides; D030421:Peroxynitrous Acid; D014443:Tyrosine; C025451:sodium bisulfide; D006862:Hydrogen Sulfide