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Hydrogen sulfide inhibits myocardial injury induced by homocysteine in rats

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An Erratum to this article was published on 29 January 2008

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.

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Acknowledgments

This work was supported by the National Natural Science Foundation of the People’s Republic China (No: 30400151), the Natural Science Foundation of Beijing (No 7052043), the Major State Basic Research Development Program of the People’s Republic of China (No. 2006CB503807) and the National Science Fund for Distinguished Young Scholars (No: 30425010).

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Authors and Affiliations

  1. Institute of Cardiovascular Research, Peking University, Xishuku Street 8, West District, 100034, Beijing, People’s Republic of China

    Lin Chang, Bin Geng & Chaoshu Tang

  2. Department of Physiology, Peking University Health Science Center, Beijing, People’s Republic of China

    Bin Geng, Fang Yu, Jing Zhao, Hongfeng Jiang & Chaoshu Tang

  3. Department of Pediatric, First Hospital of Peking University, Beijing, People’s Republic of China

    Junbao Du

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  1. Lin Chang
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  2. Bin Geng
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Correspondence to Bin Geng.

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An erratum to this article is available at http://dx.doi.org/10.1007/s00726-008-0027-8.

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Chang, L., Geng, B., Yu, F. et al. Hydrogen sulfide inhibits myocardial injury induced by homocysteine in rats. Amino Acids 34, 573–585 (2008). https://doi.org/10.1007/s00726-007-0011-8

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