title: 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.
authors.affiliation: Department of Surgery, University of Rochester Medical Center, Box SURG, 601 Elmwood Avenue, NY 14642-8410, USA.
authors.forename: Shariq
authors.initials: S
authors.lastname: Sayeed
authors.forename: John P
authors.initials: JP
authors.lastname: Cullen
authors.forename: Myra
authors.initials: M
authors.lastname: Coppage
authors.forename: James V
authors.initials: JV
authors.lastname: Sitzmann
authors.forename: Eileen M
authors.initials: EM
authors.lastname: Redmond
mesh_terms: D000818:Animals; D001013:Aorta, Thoracic / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects* / Q000502:physiology; D018797:Cell Cycle Proteins / Q000096:biosynthesis*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000494:pharmacology*; D008297:Male; D009130:Muscle, Smooth / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D018797:Cell Cycle Proteins; D000431:Ethanol