Hydrogen sulfide scavenges the cytotoxic lipid oxidation product 4-HNE.
Highly reactive alpha,beta-unsaturated aldehydes like 4-hydroxy-2-nonenal (4-HNE), generated from oxidation of polyunsaturated fatty acids, can bind to proteins, polynucleotides and exert cytotoxicity. 4-HNE is known to react readily with thiol and amino groups on free or bound amino acids. Recently, hydrogen sulfide (H(2)S) has been identified as an endogenous vascular gasotransmitter and neuromodulator which can reach up to 160 micromol/l in the brain. Markedly higher 4-HNE concentrations were reported in the brain of patients suffering from Alzheimer's disease. Assuming that the low molecular thiol H(2)S may react with 4-HNE, we have tested the ability of H(2)S to counteract the cytotoxic and protein-modifying activity of 4-HNE. The results show that H(2)S at physiologically relevant concentrations could effectively protect neuronal cells (SH-SY5Y) from the cytotoxic action of 4-HNE. The HNE-modification of cellular proteins was also inhibited in presence of H(2)S. These data suggest that H(2)S may be an important protective factor against carbonyl stress by inactivating/modulating the action of highly reactive alpha,beta-unsaturated aldehydes like 4-HNE in the brain.
Schreier
Sabine M
SM
Department of Medical Chemistry, Medical University Vienna, Waehringerstr. 10, 1090, Vienna, Austria.
Muellner
Markus K
MK
Steinkellner
Hannes
H
Hermann
Marcela
M
Esterbauer
Harald
H
Exner
Markus
M
Gmeiner
Bernhard M K
BM
Kapiotis
Stylianos
S
Laggner
Hilde
H
D000393:Air Pollutants / Q000494:pharmacology*; D000447:Aldehydes / Q000378:metabolism* / Q000494:pharmacology*; D000704:Analysis of Variance; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D024202:Electrophoretic Mobility Shift Assay / Q000379:methods; D006801:Humans; D006862:Hydrogen Sulfide / Q000494:pharmacology*; D015227:Lipid Peroxidation / Q000187:drug effects*; D009447:Neuroblastoma / Q000473:pathology
D000393:Air Pollutants; D000447:Aldehydes; C027576:4-hydroxy-2-nonenal; D006862:Hydrogen Sulfide
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