Supression of hemin-mediated oxidation of low-density lipoprotein and subsequent endothelial reactions by hydrogen sulfide (H(2)S).
Heme-mediated oxidative modification of low-density lipoprotein (LDL) plays a crucial role in early atherogenesis. It has been shown that hydrogen sulfide (H(2)S) produced by vascular smooth muscle cells is present in plasma at a concentration of about 50 micromol/L. H(2)S is a strong reductant which can react with reactive oxygen species like superoxide anion and hydrogen peroxide. The current study investigated the effect of H(2)S on hemin-mediated oxidation of LDL and oxidized LDL (oxLDL)-induced endothelial reactions. H(2)S dose dependently delayed the accumulation of lipid peroxidation products-conjugated dienes, lipid hydroperoxides (LOOH), and thiobarbituric acid reactive substances-during hemin-mediated oxidation. Moreover, H(2)S decreased the LOOH content of both oxidized LDL and lipid extracts derived from soft atherosclerotic plaque, which was accompanied by reduced cytotoxicity. OxLDL-mediated induction of the oxidative stress responsive gene, heme oxygenase-1, was also abolished by H(2)S. Finally we have shown that H(2)S can directly protect endothelium against hydrogen peroxide and oxLDL-mediated endothelial cytotoxicity. These results demonstrate novel functions of H(2)S in preventing hemin-mediated oxidative modification of LDL, and consequent deleterious effects, suggesting a possible antiatherogenic action of H(2)S.
Jeney
Viktória
V
Department of Medicine, University of Debrecen, Hungary.
Komódi
Edina
E
Nagy
Emõke
E
Zarjou
Abolfazl
A
Vercellotti
Gregory M
GM
Eaton
John W
JW
Balla
György
G
Balla
József
J
D050197:Atherosclerosis / Q000201:enzymology* / Q000473:pathology / Q000517:prevention & control; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D002460:Cell Line; D019610:Cytoprotection; D042783:Endothelial Cells / Q000378:metabolism* / Q000473:pathology; D006427:Hemin / Q000378:metabolism*; D006801:Humans; D006862:Hydrogen Sulfide / Q000494:pharmacology*; D050356:Lipid Metabolism / Q000187:drug effects; D008054:Lipid Peroxides / Q000097:blood; D008077:Lipoproteins, LDL / Q000097:blood / Q000502:physiology*; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000502:physiology; D014471:Umbilical Veins / Q000473:pathology
D008054:Lipid Peroxides; D008077:Lipoproteins, LDL; D006427:Hemin; D006862:Hydrogen Sulfide