Amino Acids

, Volume 34, Issue 4, pp 573–585

Hydrogen sulfide inhibits myocardial injury induced by homocysteine in rats

  • Lin Chang
  • Bin Geng
  • Fang Yu
  • Jing Zhao
  • Hongfeng Jiang
  • Junbao Du
  • Chaoshu Tang
Original Article

DOI: 10.1007/s00726-007-0011-8

Cite this article as:
Chang, L., Geng, B., Yu, F. et al. Amino Acids (2008) 34: 573. doi:10.1007/s00726-007-0011-8
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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 γ 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.

Keywords

Homocysteine Hydrogen sulfide Sulfur containing amino acids Oxidative stress Endoplasmic reticulum stress 

Copyright information

© Springer-Verlag 2007

Authors and Affiliations

  • Lin Chang
    • 1
  • Bin Geng
    • 1
    • 2
  • Fang Yu
    • 2
  • Jing Zhao
    • 2
  • Hongfeng Jiang
    • 2
  • Junbao Du
    • 3
  • Chaoshu Tang
    • 1
    • 2
  1. 1.Institute of Cardiovascular ResearchPeking UniversityBeijingPeople’s Republic of China
  2. 2.Department of PhysiologyPeking University Health Science CenterBeijingPeople’s Republic of China
  3. 3.Department of PediatricFirst Hospital of Peking UniversityBeijingPeople’s Republic of China

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