Oxidative stress-dependent Ras-ERK activation involves in aldosterone-induced mesangial cell proliferation
10.3760/cma.j.issn.1001-7097.2012.01.009
- VernacularTitle:氧化应激介导的Ras-ERK信号通路活化参与醛固酮诱导的肾小球系膜细胞增殖
- Author:
Fei ZHAO
;
Songming HUANG
;
Guixia DING
;
Huaying BAO
;
Ying CHEN
;
Yuan HAN
;
Weizhen ZHANG
;
Aihua ZHANG
- Publication Type:Journal Article
- Keywords:
Glomerular mesangial cells;
Aldosterone;
Reactive oxygen species;
Extracellular signal-regulated kinase
- From:
Chinese Journal of Nephrology
2012;28(1):41-46
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the role of oxidative stress-dependent Rasextracellular signal-regulated kinase (ERK1/2) signaling in aldosterone (ALDO)-induced mesangial cell proliferation. Methods The incorporation of 3H-thymidine (3H-TdR) and cell count were used as the measure of mesangial cell (MC) proliferation.Western blotting was used to detect the activation of Ki-RasA,c-Raf,MEK1/2,ERK1/2 and PI3K. Results Aldosterone significantly induced human mesangial cell proliferation,and anti-oxidant N-Acetylcysteine (NAC),catalase,and super oxide dismutase (SOD) significantly inhibited ALDO-induced mesangial cell proliferation (P＜0.01,respectively).Stimulation by ALDO for 3 h,Ki-RasA,c-Raf,MEK1/2,and ERK1/2 activity increased by 4.05-, 3.62-, 4.52-, and 3.40-fold compared with control group (P ＜0.01,respectively).NAC almost completely blocked ALDO-induced Ki-RasA,c-Raf,MEK1/2,and ERK1/2 activation (P＜0.01,respectively).Ki-RasA siRNA dose-dependently inhibited Ki-RasA expression, ALDO-induced Ki-RasA activation, and mesangial cell proliferation (P ＜0.01,respectively).c-Raf inhibitor GW5074 and MEK1/2 inhibitor PD98059 also reduced ALDO-induced mesangial cell proliferation by 65％ respectvely (P＜0.01).Ki-RasA siRNA had no effect on ALDO-induced PI3K phosphorylation.Combining LY294002 and PD98059 completely blocked ALDO-induced mesangial cell proliferation (P＜0.01). Conclusions ALDO-induced Ki-RasA-c-Raf-MEK-ERK signaling activation is dependent on reactive oxygen species (ROS) production,which mediates ALDO-induced mesangial cell proliferation.Inhibition of both ERK1/2 and PI3K signaling simultaneously completely blocks ALDO-induced mesangial cell proliferation.
