Original ArticleS-propargyl-cysteine Protects Both Adult Rat Hearts and Neonatal Cardiomyocytes From Ischemia/Hypoxia Injury: The Contribution of the Hydrogen Sulfide-Mediated PathwayWang, Qian MD, PhD*; Liu, Hong-Rui MD, PhD*; Mu, Qing PhD†; Rose, Peter PhD‡; Zhu, Yi Zhun MD, PhD*Author Information From the *Department of Pharmacology, School of Pharmacy and Institute of Biomedical Sciences, Fudan University, Shanghai, China; †Natural Product Medicinal Chemistry, School of Pharmacy, Fudan University, Shanghai, China; and ‡Pharmaceutical Science Research Division, King's College, University of London, Franklin Wilkins Building, London, UK. Received for publication March 17, 2009; accepted March 17, 2009. Supported by research grants from the National Natural Science Foundation of China (30772565), the National 973 Project (2007CB512006), the Shanghai Leading Academic Discipline Project (B119), the Shanghai-Unilever Research & Development Fund (8540750400), and the Fudan Post-Graduate Innovation Fund (EYF129001). The authors report no conflicts of interest. Reprints: Yi-Zhun Zhu, MD, PhD, 826 Zhang Heng Road, Pudong New Area, Shanghai, 200032, China (e-mail: [email protected]). Journal of Cardiovascular Pharmacology: August 2009 - Volume 54 - Issue 2 - p 139-146 doi: 10.1097/FJC.0b013e3181ac8e12 Buy Metrics Abstract 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-γ-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. © 2009 Lippincott Williams & Wilkins, Inc.