title: Hydrogen sulfide scavenges the cytotoxic lipid oxidation product 4-HNE.
abstract: 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.
authors.affiliation: Department of Medical Chemistry, Medical University Vienna, Waehringerstr. 10, 1090, Vienna, Austria.
authors.forename: Sabine M
authors.initials: SM
authors.lastname: Schreier
authors.forename: Markus K
authors.initials: MK
authors.lastname: Muellner
authors.forename: Hannes
authors.initials: H
authors.lastname: Steinkellner
authors.forename: Marcela
authors.initials: M
authors.lastname: Hermann
authors.forename: Harald
authors.initials: H
authors.lastname: Esterbauer
authors.forename: Markus
authors.initials: M
authors.lastname: Exner
authors.forename: Bernhard M K
authors.initials: BM
authors.lastname: Gmeiner
authors.forename: Stylianos
authors.initials: S
authors.lastname: Kapiotis
authors.forename: Hilde
authors.initials: H
authors.lastname: Laggner
mesh_terms: 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
chemical_list: D000393:Air Pollutants; D000447:Aldehydes; C027576:4-hydroxy-2-nonenal; D006862:Hydrogen Sulfide
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