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Ethanol differentially modulates the expression and activity of cell cycle regulatory proteins in rat aortic smooth muscle cells.

Abstract：

:The aim of this study was to determine the effect of ethanol on cell cycle events during the G(1) and S phases in cultured vascular smooth muscle cells (VSMC). Flow cytometric analysis for the DNA content in rat aortic VSMC indicated that following ethanol treatment, the cell population in the G(0)/G(1) phase increased; 57.8+/-1.6% vs. 72.3+/-1.2%, concomitant with a decrease in cells in the S phase; 12.7+/-1.4% vs. 3.67+/-0.6%, for control vs. ethanol, respectively. Western blot analysis on VSMC lysates demonstrated that ethanol (10-160 mmol/l) dose-dependently inhibited serum-induced retinoblastoma (pRb) hyperphosphorylation. While having no effect on Cdk2 protein expression, ethanol dose-dependently decreased (IC(50) approximately 60 mmol/l) Cdk2 activity, assessed by histone H1 phosphorylation. Furthermore, ethanol induced the expression of the cyclin-dependent kinase (Cdk) inhibitor p21(waf1/cip1), and inhibited the induction of cyclin A. These data demonstrate that modulation of the expression and activity of key cell cycle regulatory molecules may be a mechanism by which ethanol inhibits VSMC proliferation. These actions of ethanol may be relevant to its cardiovascular protective effect in vivo.

journal_name

Eur J Pharmacol

journal_title

European journal of pharmacology

authors

Sayeed S,Cullen JP,Coppage M,Sitzmann JV,Redmond EM

doi

10.1016/s0014-2999(02)01761-2

keywords:

subject

Has Abstract

pub_date

2002-06-12 00:00:00

pages

163-70

issue

3

eissn

0014-2999

issn

1879-0712

pii

S0014299902017612

journal_volume

445

pub_type

杂志文章

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