title: Regulator of G-protein signaling 5 protects cardiomyocytes against apoptosis during in vitro cardiac ischemia-reperfusion in mice by inhibiting both JNK1/2 and P38 signaling pathways.
abstract: Ischemic heart disease is one of the most common diseases in modern society. Ischemic myocardium can be salvaged by vascular recanalization therapy, but its benefit is attenuated by injury that can occur during reperfusion. And apoptotic cell death plays an important part in myocardial ischemia-reperfusion (IR) injury. Regulator of G-protein signaling 5 (RGS5), highly expressed in different cell types of the human adult heart, is a guanosine triphosphatase-activating protein to inhibit many signaling pathways such as c-Jun NH2-terminal kinase 1/2 (JNK1/2) and p38 which promote cardiac IR-induced apoptosis. However the role of RGS5 in cardiac IR-induced apoptosis remains unclear. An in vitro IR model was applied to the isolated hearts of wild type mice (WT), RGS5-transgenic mice (TG), and RGS5-knockout mice (KO). Our results revealed that compared with either WT or KO mice, TG mice showed inhibition of cardiomyocyte apoptosis as indicated by a greater increase of B cell lymphoma/lewkmia-2 (Bcl-2), and an obvious reduction in the positive expression of the terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL), Bcl-2 Associated X protein (Bax), and active caspase-3. Moreover, the inhibition of both JNK1/2 and p38 signaling markedly reversed IR-induced cardiomyocyte apoptosis in RGS5-KO mice. These studies show that RGS5 protects cardiomyocytes against apoptosis during IR through inhibiting both JNK1/2 and p38 signaling pathways.
authors.affiliation: Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, China; Cardiovascular Research Institute of Wuhan University, Wuhan, Hubei Province, China.
authors.forename: Zhiqiang
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, China; Cardiovascular Research Institute of Wuhan University, Wuhan, Hubei Province, China. Electronic address: wzqqzw10001@hotmail.com.
authors.forename: He
authors.initials: H
authors.lastname: Huang
authors.affiliation: Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, China; Cardiovascular Research Institute of Wuhan University, Wuhan, Hubei Province, China.
authors.forename: Wangwei
authors.initials: W
authors.lastname: He
authors.affiliation: Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, China; Cardiovascular Research Institute of Wuhan University, Wuhan, Hubei Province, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Kong
authors.affiliation: Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, China; Cardiovascular Research Institute of Wuhan University, Wuhan, Hubei Province, China.
authors.forename: He
authors.initials: H
authors.lastname: Hu
authors.affiliation: Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, China; Cardiovascular Research Institute of Wuhan University, Wuhan, Hubei Province, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Fan
authors.affiliation: Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, China; Cardiovascular Research Institute of Wuhan University, Wuhan, Hubei Province, China.
authors.forename: Jiafen
authors.initials: J
authors.lastname: Liao
authors.affiliation: Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, China; Cardiovascular Research Institute of Wuhan University, Wuhan, Hubei Province, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, China; Cardiovascular Research Institute of Wuhan University, Wuhan, Hubei Province, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Mei
authors.affiliation: Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, China; Cardiovascular Research Institute of Wuhan University, Wuhan, Hubei Province, China.
authors.forename: Wanli
authors.initials: W
authors.lastname: Liu
authors.affiliation: Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, China; Cardiovascular Research Institute of Wuhan University, Wuhan, Hubei Province, China.
authors.forename: Xiaoju
authors.initials: X
authors.lastname: Xiong
authors.affiliation: Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, China; Cardiovascular Research Institute of Wuhan University, Wuhan, Hubei Province, China.
authors.forename: Jianye
authors.initials: J
authors.lastname: Peng
authors.affiliation: Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, China; Cardiovascular Research Institute of Wuhan University, Wuhan, Hubei Province, China.
authors.forename: Yali
authors.initials: Y
authors.lastname: Xiao
authors.affiliation: Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, China; Cardiovascular Research Institute of Wuhan University, Wuhan, Hubei Province, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Huang
authors.affiliation: Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, China; Cardiovascular Research Institute of Wuhan University, Wuhan, Hubei Province, China.
authors.forename: Dajun
authors.initials: D
authors.lastname: Quan
authors.affiliation: Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, China; Cardiovascular Research Institute of Wuhan University, Wuhan, Hubei Province, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Li
authors.affiliation: Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, China; Cardiovascular Research Institute of Wuhan University, Wuhan, Hubei Province, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Xiong
authors.affiliation: Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, China; Cardiovascular Research Institute of Wuhan University, Wuhan, Hubei Province, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Zhong
authors.affiliation: Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, China; Cardiovascular Research Institute of Wuhan University, Wuhan, Hubei Province, China.
authors.forename: Guangji
authors.initials: G
authors.lastname: Wang
mesh_terms: D000818:Animals; D017209:Apoptosis; D020935:MAP Kinase Signaling System; D008297:Male; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D048055:Mitogen-Activated Protein Kinase 8 / Q000378:metabolism*; D048056:Mitogen-Activated Protein Kinase 9 / Q000378:metabolism*; D017202:Myocardial Ischemia / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D032383:Myocytes, Cardiac / Q000378:metabolism / Q000473:pathology*; D020710:RGS Proteins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D020710:RGS Proteins; C105346:Rgs5 protein, mouse; D048056:Mitogen-Activated Protein Kinase 9; D048055:Mitogen-Activated Protein Kinase 8
keywords: Apoptosis; Ischemia-reperfusion; JNK1/2; RGS5; p38