PMID- 18071843 OWN - NLM STAT- MEDLINE DCOM- 20080815 LR - 20211203 IS - 1438-2199 (Electronic) IS - 0939-4451 (Linking) VI - 34 IP - 4 DP - 2008 May TI - Hydrogen sulfide inhibits myocardial injury induced by homocysteine in rats. PG - 573-85 AB - 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. FAU - Chang, Lin AU - Chang L AD - Institute of Cardiovascular Research, Peking University, Xishuku Street 8, West District, 100034 Beijing, People's Republic of China. FAU - Geng, Bin AU - Geng B FAU - Yu, Fang AU - Yu F FAU - Zhao, Jing AU - Zhao J FAU - Jiang, Hongfeng AU - Jiang H FAU - Du, Junbao AU - Du J FAU - Tang, Chaoshu AU - Tang C LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20071211 PL - Austria TA - Amino Acids JT - Amino acids JID - 9200312 RN - 0 (Endoplasmic Reticulum Chaperone BiP) RN - 0 (Heat-Shock Proteins) RN - 0 (Molecular Chaperones) RN - 0 (RNA, Messenger) RN - 0 (Reactive Oxygen Species) RN - 0LVT1QZ0BA (Homocysteine) RN - 11062-77-4 (Superoxides) RN - BBX060AN9V (Hydrogen Peroxide) RN - EC 1.15.1.1 (Superoxide Dismutase) RN - EC 1.3.99.1 (Succinate Dehydrogenase) RN - EC 1.9.3.1 (Electron Transport Complex IV) RN - EC 4.4.1.1 (Cystathionine gamma-Lyase) RN - YY9FVM7NSN (Hydrogen Sulfide) SB - IM EIN - Amino Acids. 2008 May;34(4):687 MH - Animals MH - Cystathionine gamma-Lyase/*drug effects/metabolism MH - Disease Models, Animal MH - Electron Transport Complex IV/drug effects/metabolism MH - Endoplasmic Reticulum/drug effects/metabolism MH - Endoplasmic Reticulum Chaperone BiP MH - Enzyme Activation/drug effects MH - Heart Diseases/*prevention & control MH - Heat-Shock Proteins/drug effects/genetics MH - Homocysteine/blood/*toxicity MH - Hydrogen Peroxide/metabolism MH - Hydrogen Sulfide/metabolism/pharmacology/*therapeutic use MH - Lipid Peroxidation/drug effects MH - Male MH - Mitochondria, Heart/drug effects/enzymology/metabolism MH - Molecular Chaperones/drug effects/genetics MH - Myocardium/*metabolism/pathology MH - RNA, Messenger/metabolism MH - Rats MH - Rats, Sprague-Dawley MH - Reactive Oxygen Species/antagonists & inhibitors/metabolism MH - Reverse Transcriptase Polymerase Chain Reaction MH - Succinate Dehydrogenase/drug effects/metabolism MH - Superoxide Dismutase/drug effects/metabolism MH - Superoxides/metabolism MH - Time Factors EDAT- 2007/12/12 09:00 MHDA- 2008/08/16 09:00 CRDT- 2007/12/12 09:00 PHST- 2007/10/12 00:00 [received] PHST- 2007/11/17 00:00 [accepted] PHST- 2007/12/12 09:00 [pubmed] PHST- 2008/08/16 09:00 [medline] PHST- 2007/12/12 09:00 [entrez] AID - 10.1007/s00726-007-0011-8 [doi] PST - ppublish SO - Amino Acids. 2008 May;34(4):573-85. doi: 10.1007/s00726-007-0011-8. Epub 2007 Dec 11.