S-propargyl-cysteine protects both adult rat hearts and neonatal cardiomyocytes from ischemia/hypoxia injury: the contribution of the hydrogen sulfide-mediated pathway.
In this study, we determined the cardioprotective effects of S-propargyl-cysteine (SPRC), a structural analog of S-allylcysteine (SAC), using in vivo models of acute myocardial infarction (MI) and in vitro hypoxic cardiomyocytes models. MI was created in rats by ligating the left anterior descending coronary artery. Plasma enzymes levels and cystathionine-gamma-lyase (CSE) activities were determined. Primary cultures of newborn rats' cardiomyocytes were injured by hypoxia for 6 h. Cell viabilities were measured with the thiazolyl blue assay. RT-PCR and western blot analysis revealed the expression of CSE in both models. The protective effects of SPRC were associated with an observed reduction in infarct size (20.8 +/- 2.4% vs. 36.0 +/- 1.3%), decreased plasma enzymes levels and reduced malondialdehyde levels when compared to the MI vehicle group (P < 0.05); cardiac function was also improved. SPRC increased CSE activity and plasma H2S concentration by 1.6-fold and 1.3-fold, respectively, in MI rats. Decreased cell viability (64.5 +/- 5.4%) in hypoxic cardiomyocytes could be rescued with use of SPRC (81.0 +/- 3.1%). Similarly, mRNA and protein expression of CSE were upregulated in the SPRC group. Treatment with the CSE inhibitor propargylglycine abolished the protective effects of SPRC. Our study provides novel evidence that SPRC is protective in myocardial infarctions via a H2S-related pathway.
Wang
Qian
Q
Department of Pharmacology, School of Pharmacy and Institute of Biomedical Sciences, Fudan University, Shanghai, China.
Liu
Hong-Rui
HR
Mu
Qing
Q
Rose
Peter
P
Zhu
Yi Zhun
YZ
D000818:Animals; D000831:Animals, Newborn; D015687:Cell Hypoxia; D002470:Cell Survival / Q000187:drug effects; D003542:Cystathionine gamma-Lyase / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D003545:Cysteine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D004195:Disease Models, Animal; D006862:Hydrogen Sulfide / Q000378:metabolism*; D008297:Male; D009203:Myocardial Infarction / Q000503:physiopathology / Q000517:prevention & control*; D017202:Myocardial Ischemia / Q000503:physiopathology / Q000517:prevention & control*; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015854:Up-Regulation / Q000187:drug effects
C556437:S-propargylcysteine; D003542:Cystathionine gamma-Lyase; D003545:Cysteine; D006862:Hydrogen Sulfide