Reactive oxygen species in mechanical stress-induced cardiac hypertrophy

被引：112

作者：

Aikawa, R

Nagai, T

Tanaka, M

Zou, YZ

Ishihara, T

Takano, H

Hasegawa, H

Akazawa, H

Mizukami, M

Nagai, R

Komuro, I

机构：

[1] Chiba Univ, Grad Sch Med, Dept Cardiovasc Sci & Med, Chuo Ku, Chiba 2608670, Japan

[2] Univ Tokyo, Grad Sch Med, Dept Cardiovasc Med, Tokyo, Japan

[3] Tohoku Univ, Grad Sch Med, Dept Metab Dis, Sendai, Miyagi, Japan

来源：

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 2001年 / 289卷 / 04期

关键词：

hypertrophy; cardiomyocyte; mechanical stress; signal transduction; small GTP-binding protein; rhoA; rac1; cdc42; reactive oxygen species; p38MAPK;

D O I：

10.1006/bbrc.2001.6068

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Mechanical stress induces various hypertrophic responses including activation of mitogen-activated protein kinases (MAPKs) in cardiac myocytes. Here we examined the role of the small GTP-binding proteins of Rho family and reactive oxygen species (ROS) in stretch-induced activation of p38MAPK in cardiomyocytes. Overexpression of dominant-negative mutants of Rac1 (D.N. Rac1), D.N.RhoA and D.N.Cdc42 suppressed stretch-induced activation of p38MAPK. Overexpression of constitutively active mutants of Rac1 (C.A.Rac1) and C.A.Cdc42 increased the p38MAPK activity in the absence of mechanical stress. Pretreatment with N-acetyl-L-cysteine and N-(2-mercaptopropionyl)-glycine (NAC) suppressed stretch-induced activation of p38MAPH. Mechanical stretch increased intracellular ROS generation, which was abrogated by overexpression of D.N.Rac1 and attenuated by overexpression of D.N.RhoA and DN.Cdc42. An increase in protein synthesis evoked by mechanical stretch was suppressed by overexpression of DN.Rac1 and pretreatment with NAC. These results suggest that mechanical stress induces cardiac hypertrophy through the Rac1-ROS-p38MAPK pathway in cardiac myocytes. (C) 2001 Elsevier Science.

引用

页码：901 / 907

页数：7