PMID- 27021681 OWN - NLM STAT- MEDLINE DCOM- 20160829 LR - 20160418 IS - 1090-2104 (Electronic) IS - 0006-291X (Linking) VI - 473 IP - 2 DP - 2016 Apr 29 TI - 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. PG - 551-7 LID - S0006-291X(16)30427-2 [pii] LID - 10.1016/j.bbrc.2016.03.114 [doi] AB - 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. CI - Copyright (c) 2016 Elsevier Inc. All rights reserved. FAU - Wang, Zhiqiang AU - Wang Z AD - Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, China; Cardiovascular Research Institute of Wuhan University, Wuhan, Hubei Province, China. FAU - Huang, He AU - Huang H AD - 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. FAU - He, Wangwei AU - He W AD - Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, China; Cardiovascular Research Institute of Wuhan University, Wuhan, Hubei Province, China. FAU - Kong, Bin AU - Kong B AD - Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, China; Cardiovascular Research Institute of Wuhan University, Wuhan, Hubei Province, China. FAU - Hu, He AU - Hu H AD - Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, China; Cardiovascular Research Institute of Wuhan University, Wuhan, Hubei Province, China. FAU - Fan, Yang AU - Fan Y AD - Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, China; Cardiovascular Research Institute of Wuhan University, Wuhan, Hubei Province, China. FAU - Liao, Jiafen AU - Liao J AD - Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, China; Cardiovascular Research Institute of Wuhan University, Wuhan, Hubei Province, China. FAU - Wang, Lei AU - Wang L AD - Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, China; Cardiovascular Research Institute of Wuhan University, Wuhan, Hubei Province, China. FAU - Mei, Yang AU - Mei Y AD - Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, China; Cardiovascular Research Institute of Wuhan University, Wuhan, Hubei Province, China. FAU - Liu, Wanli AU - Liu W AD - Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, China; Cardiovascular Research Institute of Wuhan University, Wuhan, Hubei Province, China. FAU - Xiong, Xiaoju AU - Xiong X AD - Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, China; Cardiovascular Research Institute of Wuhan University, Wuhan, Hubei Province, China. FAU - Peng, Jianye AU - Peng J AD - Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, China; Cardiovascular Research Institute of Wuhan University, Wuhan, Hubei Province, China. FAU - Xiao, Yali AU - Xiao Y AD - Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, China; Cardiovascular Research Institute of Wuhan University, Wuhan, Hubei Province, China. FAU - Huang, Dan AU - Huang D AD - Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, China; Cardiovascular Research Institute of Wuhan University, Wuhan, Hubei Province, China. FAU - Quan, Dajun AU - Quan D AD - Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, China; Cardiovascular Research Institute of Wuhan University, Wuhan, Hubei Province, China. FAU - Li, Qi AU - Li Q AD - Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, China; Cardiovascular Research Institute of Wuhan University, Wuhan, Hubei Province, China. FAU - Xiong, Liang AU - Xiong L AD - Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, China; Cardiovascular Research Institute of Wuhan University, Wuhan, Hubei Province, China. FAU - Zhong, Peng AU - Zhong P AD - Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, China; Cardiovascular Research Institute of Wuhan University, Wuhan, Hubei Province, China. FAU - Wang, Guangji AU - Wang G AD - Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, China; Cardiovascular Research Institute of Wuhan University, Wuhan, Hubei Province, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20160325 PL - United States TA - Biochem Biophys Res Commun JT - Biochemical and biophysical research communications JID - 0372516 RN - 0 (RGS Proteins) RN - 0 (Rgs5 protein, mouse) RN - EC 2.7.1.24 (Mitogen-Activated Protein Kinase 9) RN - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 8) SB - IM MH - Animals MH - Apoptosis MH - *MAP Kinase Signaling System MH - Male MH - Mice, Inbred C57BL MH - Mice, Knockout MH - Mitogen-Activated Protein Kinase 8/*metabolism MH - Mitogen-Activated Protein Kinase 9/*metabolism MH - Myocardial Ischemia/genetics/*metabolism/pathology MH - Myocytes, Cardiac/metabolism/*pathology MH - RGS Proteins/genetics/*metabolism MH - *Signal Transduction OTO - NOTNLM OT - Apoptosis OT - Ischemia-reperfusion OT - JNK1/2 OT - RGS5 OT - p38 EDAT- 2016/03/30 06:00 MHDA- 2016/08/30 06:00 CRDT- 2016/03/30 06:00 PHST- 2016/03/23 00:00 [received] PHST- 2016/03/23 00:00 [accepted] PHST- 2016/03/30 06:00 [entrez] PHST- 2016/03/30 06:00 [pubmed] PHST- 2016/08/30 06:00 [medline] AID - S0006-291X(16)30427-2 [pii] AID - 10.1016/j.bbrc.2016.03.114 [doi] PST - ppublish SO - Biochem Biophys Res Commun. 2016 Apr 29;473(2):551-7. doi: 10.1016/j.bbrc.2016.03.114. Epub 2016 Mar 25.