title: SPRC protects hypoxia and re-oxygenation injury by improving rat cardiac contractile function and intracellular calcium handling.
abstract: 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 Ca(2+) ([Ca(2+)]i) was measured using specific dyes and detected by digital imaging apparatus. Apoptotic cells were evaluated by TUNEL assay. Intervention with SPRC (10 μM) 30 min 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 ([Ca(2+)]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 Ca(2+) handling during the H/R. Furthermore, the protective effect of SPRC can be partly blocked by CSE inhibitor PAG.
authors.affiliation: Department of Pharmacology, School of Pharmacy, Fudan University, Shanghai 201203, China.
authors.forename: Yong-Hua
authors.initials: YH
authors.lastname: Liang
authors.affiliation: Department of Pharmacology, School of Pharmacy, Fudan University, Shanghai 201203, China.
authors.forename: Ya-Qi
authors.initials: YQ
authors.lastname: Shen
authors.affiliation: Department of Pharmacology, School of Pharmacy, Fudan University, Shanghai 201203, China. Electronic address: guowei@fudan.edu.cn.
authors.forename: Wei
authors.initials: W
authors.lastname: Guo
authors.affiliation: Department of Pharmacology, School of Pharmacy, Fudan University, Shanghai 201203, China; Department of Pharmacology, Yong Loo Lin School of Medicine, Clinical Research Centre, National University of Singapore, Singapore. Electronic address: zhuyz@fudan.edu.cn.
authors.forename: Yi-Zhun
authors.initials: YZ
authors.lastname: Zhu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002118:Calcium / Q000378:metabolism*; D015687:Cell Hypoxia / Q000187:drug effects*; D048430:Cell Shape / Q000187:drug effects; D002478:Cells, Cultured; D003545:Cysteine / Q000031:analogs & derivatives* / Q000494:pharmacology; D042541:Intracellular Space / Q000378:metabolism; D008297:Male; D032383:Myocytes, Cardiac / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D010100:Oxygen / Q000378:metabolism; D010210:Papillary Muscles / Q000166:cytology / Q000187:drug effects; D020011:Protective Agents / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D020011:Protective Agents; C556437:S-propargylcysteine; D003545:Cysteine; D010100:Oxygen; D002118:Calcium
keywords: Ca(2+); Hypoxia and re-oxygenation; Isolated papillary muscles; Isolated ventricular myocytes; S-Propargyl-l-cysteine