Hydrogen sulphide: a novel inhibitor of hypochlorous acid-mediated oxidative damage in the brain?
Hydrogen sulphide (H(2)S) is a cytotoxic gas that has recently been proposed as a novel neuromodulator. Endogenous levels of H(2)S in the brain range between 50 and 160 microM, and considerably lower H(2)S levels are reported in the brains of Alzheimer's disease (AD) patients. Levels of myeloperoxidase (MPO), an enzyme that catalyses the formation of the oxidant hypochlorous acid (HOCl), are elevated in the prefrontal cortex, hippocampal microglia, and neurons of AD patients where MPO co-localised with beta-amyloid plaques. Recently 3-chlorotyrosine, a bio-marker for MPO activity (and HOCl production), was shown to be elevated threefold in hippocampal proteins from AD patients. Since H(2)S and HOCl are important mediators in brain function and disease, we investigated the effects of H(2)S on HOCl-mediated damage to bio-molecules and to cultured human SH-SY5Y cells. H(2)S significantly inhibited HOCl-mediated inactivation of alpha(1)-antiproteinase and protein oxidation to a comparable extent to reduced glutathione. H(2)S also inhibited HOCl-induced cytotoxicity, intracellular protein oxidation, and lipid peroxidation in SH-SY5Y cells. These data suggest that H(2)S has the potential to act as an inhibitor of HOCl-mediated processes in vivo and that the potential antioxidant action of H(2)S deserves further study, especially since extracellular GSH levels in the brain are very low.
Whiteman
Matthew
M
Department of Biochemistry, Faculty of Medicine, National University of Singapore, 8 Medical Drive, Singapore 117597, Singapore. bchwml@nus.edu.sg
Cheung
Nam Sang
NS
Zhu
Yi-Zhun
YZ
Chu
Siew Hwa
SH
Siau
Jia Ling
JL
Wong
Boon Seng
BS
Armstrong
Jeffrey S
JS
Moore
Philip K
PK
D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005978:Glutathione / Q000494:pharmacology; D006801:Humans; D006862:Hydrogen Sulfide / Q000494:pharmacology*; D006997:Hypochlorous Acid / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D010084:Oxidation-Reduction / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects*
D006997:Hypochlorous Acid; D005978:Glutathione; D006862:Hydrogen Sulfide