title: Rad GTPase induces cardiomyocyte apoptosis through the activation of p38 mitogen-activated protein kinase.
abstract: Rad is a member of a subclass of small GTP-binding proteins, the RGK family. In the present study we investigated the role of Rad protein in regulating cardiomyocyte viability. DNA fragmentation and TUNEL assays demonstrated that Rad promoted rat neonatal cardiomyocyte apoptosis. Rad silencing fully blocked serum deprivation induced apoptosis, indicating Rad is necessary for trigger cardiomyocyte apoptosis. Rad overexpression caused a dramatic decrease of the anti-apoptotic molecule Bcl-x(L), whereas Bcl-x(L) overexpression protected cardiomyocytes against Rad-induced apoptosis. Rad-triggered apoptosis was mediated by the activation of p38 MAPK. The p38 blocker SB203580 effectively protected cardiomyocytes against Rad-evoked apoptosis.
authors.affiliation: Department of Cardiology, Peking University Third Hospital, Beijing, China.
authors.forename: Zhongcui
authors.initials: Z
authors.lastname: Sun
authors.forename: Ji
authors.initials: J
authors.lastname: Zhang
authors.forename: Jifeng
authors.initials: J
authors.lastname: Zhang
authors.forename: Chunlei
authors.initials: C
authors.lastname: Chen
authors.forename: Quan
authors.initials: Q
authors.lastname: Du
authors.forename: Lin
authors.initials: L
authors.lastname: Chang
authors.forename: Chunmei
authors.initials: C
authors.lastname: Cao
authors.forename: Ming
authors.initials: M
authors.lastname: Zheng
authors.forename: Minerva T
authors.initials: MT
authors.lastname: Garcia-Barrio
authors.forename: Yuqing E
authors.initials: YE
authors.lastname: Chen
authors.forename: Rui-Ping
authors.initials: RP
authors.lastname: Xiao
authors.forename: Jieming
authors.initials: J
authors.lastname: Mao
authors.forename: Xiaojun
authors.initials: X
authors.lastname: Zhu
mesh_terms: D000818:Animals; D017209:Apoptosis; D002470:Cell Survival; D002478:Cells, Cultured; D007093:Imidazoles / Q000494:pharmacology; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000201:enzymology* / Q000502:physiology*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D034741:RNA, Small Interfering / Q000235:genetics; D051381:Rats; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D018631:ras Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D007093:Imidazoles; D047428:Protein Kinase Inhibitors; D011725:Pyridines; D034741:RNA, Small Interfering; C490031:Rrad protein, rat; D048051:p38 Mitogen-Activated Protein Kinases; D018631:ras Proteins; C093642:SB 203580