SPRC protects hypoxia and re-oxygenation injury by improving rat cardiac contractile function and intracellular calcium handling

被引:11
作者
Liang, Yong-Hua [1 ]
Shen, Ya-Qi [1 ]
Guo, Wei [1 ]
Zhu, Yi-Zhun [1 ,2 ]
机构
[1] Fudan Univ, Sch Pharm, Dept Pharmacol, Shanghai 201203, Peoples R China
[2] Natl Univ Singapore, Clin Res Ctr, Yong Loo Lin Sch Med, Dept Pharmacol, Singapore 117548, Singapore
来源
NITRIC OXIDE-BIOLOGY AND CHEMISTRY | 2014年 / 41卷
关键词
Ca2+; Hypoxia and re-oxygenation; S-Propargyl-L-cysteine; Isolated papillary muscles; Isolated ventricular myocytes; REPERFUSION INJURY; SARCOPLASMIC-RETICULUM; VENTRICULAR MYOCYTES; MYOCARDIAL-ISCHEMIA; NA+/CA2+ EXCHANGER; CELL-DEATH; CARDIOMYOCYTES; CA2+; APOPTOSIS; HEART;
D O I
10.1016/j.niox.2014.05.010
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
S-Propargyl-L-cysteine (SPRC, also named as ZYZ-802) is a new compound synthesized in our lab. We investigated whether SPRC has exerted protective effects against cardiac hypoxia/re-oxygenation (H/R) and also explored its mechanisms. In our study, isolated ventricular myocytes were subject to a simulated hypoxia solution for 30 min to induce cell injury. Intracellular concentration of Ca2+ ([Ca2+]i) was measured using specific dyes and detected by digital imaging apparatus. Apoptotic cells were evaluated by TUNEL assay. Intervention with SPRC (10 mu M) 30min before hypoxia, can significantly attenuate the apoptosis of isolated papillary muscles resulting from the H/R injury and protect morphology of the muscles. In isolated ventricular myocytes, SPRC considerably improved left ventricular functional recovery. SPRC also suppressed the increase of ([Ca2+]i) during hypoxia stage. By measuring the calcium transient of the cell we concluded that SPRC can preserve the RyR and SERCA activities and improve Ca2+ handling during the H/R. Furthermore, the protective effect of SPRC can be partly blocked by CSE inhibitor PAG. (C) 2014 Elsevier Inc. All rights reserved.
引用
收藏
页码:113 / 119
页数:7
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