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Responses of vascular smooth muscle cells to estrogen are dependent on balance between ERK and p38 MAPK pathway activities.

Abstract：

OBJECTIVE:To investigate the mechanisms underlying the dual effects of estrogen on vascular smooth muscle cells (VSMC). METHODS:MTT assay, ELISA, flow cytometry and Western analysis were used to investigate the effects of 17beta-estradiol (E(2)) on proliferation, apoptosis, cell cycle progression, ERK and p38 activities of subcultured rat VSMC with or without chemical block of MEK or p38 kinases. RESULTS:E(2)-promoted VSMC proliferation was accompanied with an increased phosphorylation of ERK1/2, which could be blocked by MEK inhibitor U0126; the E(2)-induced VSMC apoptosis, which appeared mainly in the G2/M phase, was related with the activation of p38 and could be blocked by p38 inhibitor SB203580. More interestingly, MEK inhibition in E(2)-treated VSMC led to an enhanced p38 phosphorylation and a shift of apoptosis from G2/M phase-predominant to G0/G1 phase-predominant; whereas block of p38 increased the E(2)-induced ERK1/2 phosphorylation and proliferation of the VSMC. This reciprocal phenomenon was related with cross-talk between ERK and p38 pathways which might be mediated by MKP-1 and PP2A. The effects of E(2) on proliferation and apoptosis, and their related pathways could be separately induced by the specific agonists of estrogen receptor (ER) alpha and beta alone and inhibited or eliminated by the ER blocker ICI 182,780. CONCLUSION:The dual effects of estrogen on VSMC involve concurrent activations of ERK and p38 pathways by ER alpha and beta respectively, and the fates of VSMC are determined by the dynamic balance between these two pathways.

journal_name

Int J Cardiol

journal_title

International journal of cardiology

authors

Cheng B,Song J,Zou Y,Wang Q,Lei Y,Zhu C,Hu C

doi

10.1016/j.ijcard.2008.02.017

subject

Has Abstract

pub_date

2009-05-29 00:00:00

pages

356-65

issue

3

eissn

0167-5273

issn

1874-1754

pii

S0167-5273(08)00449-X

journal_volume

134

pub_type

杂志文章

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