Hydrogen Sulfide Scavenges the Cytotoxic Lipid Oxidation Product 4-HNE

Highly reactive α,β-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 μmol/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 α,β-unsaturated aldehydes like 4-HNE in the brain.