p38 mitogen-activated protein kinase mediates a negative inotropic   effect in cardiac myocytes

doi:10.1161/hh0202.104220

CORC > 北京大学 > 生命科学学院

	p38 mitogen-activated protein kinase mediates a negative inotropic effect in cardiac myocytes
	Liao, P ; Wang, SQ ; Wang, S ; Zheng, M ; Zheng, M ; Zhang, SJ ; Cheng, H ; Wang, Y ; Xiao, RP
刊名	circulation research
	2002
关键词	p38 mitogen-activated protein kinase cardiac contractility excitation-contraction coupling troponin I intracellular pH N-TERMINAL KINASES STRESS-RESPONSE PERFUSED HEART MAP KINASES RAT HEARTS INHIBITION PATHWAY PHOSPHORYLATION HYPERTROPHY APOPTOSIS
DOI	10.1161/hh0202.104220
英文摘要	p38 Mitogen-activated protein kinase (MAPK) is one of the most ancient signaling molecules and is involved in multiple cellular processes, including cell proliferation, cell growth, and cell death. In the heart, enhanced activation of p38 MAPK is associated with ischemia/reperfusion injury and the onset of heart failure. In the present study, we investigated the function of p38 MAPK in regulating cardiac contractility and its underlying mechanisms. In cultured adult rat cardiomyocytes, activation of p38 MAPK by adenoviral gene transfer of an activated mutant of its upstream kinase, MKK3bE, led to a significant reduction in baseline contractility, compared with uninfected cells or those infected with a control adenoviral vector (Adv-beta-galactosidase). The inhibitory effect of MKK3bE on contractility was largely prevented by coexpressing a dominant-negative mutant of p38 MAPK or treating cells with a p38 MAPK inhibitor, SB203580. Conversely, inhibition of endogenous p38 MAPK activity by SB203580 rapidly and reversibly enhanced cell contractility in a dose-dependent manner, without altering L-type Ca2+ currents or Ca-i(2+) transients. MKK3bE-induced p38 activation had no significant effect on pH;, whereas SB203580 had a minor effect to elevate pH,. Furthermore, activation of p38 MAPK was unable to increase troponin I phosphorylation. Thus, we conclude that the negative inotropic effect of p38 MAPK is mediated by decreasing myofilament response to Ca2+, rather than by altering Ca-i(2+) homeostasis and that the reduced myofilament Ca2+ sensitivity is unlikely attributable to troponin I phosphorylation or alterations in pH(i). These findings reveal a novel function of p38 MAPK and shed a new light on our understanding of the coincidence of p38 MAPK activation and the onset of heart failure.; Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease; SCI(E); 115; ARTICLE; 2; 190-196; 90
语种	英语
内容类型	期刊论文
源URL	[http://ir.pku.edu.cn/handle/20.500.11897/388614]
专题	生命科学学院
推荐引用方式 GB/T 7714	Liao, P,Wang, SQ,Wang, S,et al. p38 mitogen-activated protein kinase mediates a negative inotropic effect in cardiac myocytes[J]. circulation research,2002.
APA	Liao, P.,Wang, SQ.,Wang, S.,Zheng, M.,Zheng, M.,...&Xiao, RP.(2002).p38 mitogen-activated protein kinase mediates a negative inotropic effect in cardiac myocytes.circulation research.
MLA	Liao, P,et al."p38 mitogen-activated protein kinase mediates a negative inotropic effect in cardiac myocytes".circulation research (2002).