title: Hydrogen sulfide inhibits myocardial injury induced by homocysteine in rats.
abstract: Hyperhomocysteinemia (HHcy) is a critical independent risk factor for cardiovascular diseases. However, to date, no satisfactory strategies to prevent HHcy exist. Since homocysteine (Hcy) and endogenous H2S are both metabolites of sulfur-containing amino acids, we aimed to investigate whether a metabolic product of Hcy and H2S, may antagonize in part the cardiovascular effects of Hcy. In the HHcy rat model injected subcutaneously with Hcy for 3 weeks, H2S levels and the H2S-generating enzyme cystathionine gamma lyase (CSE) activity in the myocardium were decreased. The intraperitoneal injection of H2S gas saturation solution significantly reduced plasma total Hcy (tHcy) concentration and decreased lipid peroxidation formation (i.e., lowered manodialdehyde and conjugated diene levels in myocardia and plasma). The activities of myocardial mitochondrial respiratory enzymes succinate dehydrogenase, cytochrome oxidase, and manganese superoxide dismutase, related to reactive oxygen species metabolism, were significantly dysfunctional in HHcy rats. The H2S administration restored the level of enzyme activities and accelerated the scavenging of H2O2 and superoxide anion generated by Hcy in isolated mitochondria. The H2S treatment also inhibited the expression of glucose-regulated protein 78, a marker of endoplasmic reticulum (ER) stress, induced by Hcy in vivo and in vitro. Thus, HHcy impaired the myocardial CSE/H2S pathway, and the administration of H2S protected the myocardium from oxidative and ER stress induced by HHcy, which suggests that an endogenous metabolic balance of sulfur-containing amino acids may be a novel strategy for treatment of HHcy.
authors: Institute of Cardiovascular Research, Peking University, Xishuku Street 8, West District, 100034 Beijing, People's Republic of China.
authors: Lin
authors: L
authors: Chang
authors: Bin
authors: B
authors: Geng
authors: Fang
authors: F
authors: Yu
authors: Jing
authors: J
authors: Zhao
authors: Hongfeng
authors: H
authors: Jiang
authors: Junbao
authors: J
authors: Du
authors: Chaoshu
authors: C
authors: Tang
mesh_terms: D000818:Animals; D003542:Cystathionine gamma-Lyase / Q000187:drug effects* / Q000378:metabolism; D004195:Disease Models, Animal; D003576:Electron Transport Complex IV / Q000187:drug effects / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism; D000091342:Endoplasmic Reticulum Chaperone BiP; D004789:Enzyme Activation / Q000187:drug effects; D006331:Heart Diseases / Q000517:prevention & control*; D006360:Heat-Shock Proteins / Q000187:drug effects / Q000235:genetics; D006710:Homocysteine / Q000097:blood / Q000633:toxicity*; D006861:Hydrogen Peroxide / Q000378:metabolism; D006862:Hydrogen Sulfide / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use*; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008929:Mitochondria, Heart / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D018832:Molecular Chaperones / Q000187:drug effects / Q000235:genetics; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000037:antagonists & inhibitors / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013385:Succinate Dehydrogenase / Q000187:drug effects / Q000378:metabolism; D013482:Superoxide Dismutase / Q000187:drug effects / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism; D013997:Time Factors
chemical_list: D000091342:Endoplasmic Reticulum Chaperone BiP; D006360:Heat-Shock Proteins; D018832:Molecular Chaperones; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D006710:Homocysteine; D013481:Superoxides; D006861:Hydrogen Peroxide; D013482:Superoxide Dismutase; D013385:Succinate Dehydrogenase; D003576:Electron Transport Complex IV; D003542:Cystathionine gamma-Lyase; D006862:Hydrogen Sulfide