Estrogen accelerates G1 to S phase transition and induces a G2/M phase-predominant apoptosis in synthetic vascular smooth muscle cells.
OBJECTIVE
To investigate the mechanisms underlying the vascular-protective effects of estrogen.


METHODS
The synthetic (subcultured for 3-4 passages) rat vascular smooth muscle cells were exposed to gradient concentrations (10(-10)-10(-5) M) of 17beta-estradiol. The growth, cell cycle progression and apoptosis of the cells, and the related proteins including Cyclin D1, Cdk4, p38, Bax and Bcl-2 were analyzed in MTT, flow cytometry, ELISA or Western blot.


RESULTS
17beta-estradiol in the physiological concentrations (10(-10)-10(-8) M) promoted the smooth muscle cell growth in a concentration-dependent manner, accelerated transition of the cells from G1 to S phases, and up-regulated expressions of Cyclin D1 and Cdk4. Meanwhile, the hormone (10(-9)-10(-7) M) triggered a G2/M phase-predominant apoptosis of the cells in a concentration- and time-dependent manner, which was accompanied by increased phosphorylation of p38 and expression of Bax.


CONCLUSIONS
The effect of estrogen on the synthetic vascular smooth muscle cell is dual. It promotes proliferation of the cells by accelerating their G1/S phase transition via up-regulating Cyclin D1 and Cdk4; and on the other hand, it induces apoptosis of the proliferating cells by up-regulating Bax through p38-MAPK pathway.
Yang
Zhaohui
Z
Department of Anatomy and Embryology, Wuhan University School of Medicine, Wuhan, PR China.
Cheng
Bei
B
Song
Jian
J
Wan
Yu
Y
Wang
Qiao
Q
Cheng
Bangchang
B
Chen
Xichang
X
D000704:Analysis of Variance; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D002453:Cell Cycle / Q000187:drug effects* / Q000502:physiology; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D019938:Cyclin D1 / Q000032:analysis; D051358:Cyclin-Dependent Kinase 4 / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004967:Estrogens / Q000494:pharmacology*; D005260:Female; D005434:Flow Cytometry; D016193:G1 Phase / Q000187:drug effects; D016195:G2 Phase / Q000187:drug effects; D023421:Models, Animal; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000502:physiology; D011336:Probability; D051381:Rats; D017207:Rats, Sprague-Dawley; D016196:S Phase / Q000187:drug effects; D012680:Sensitivity and Specificity; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D004967:Estrogens; D019938:Cyclin D1; D051358:Cyclin-Dependent Kinase 4; D048051:p38 Mitogen-Activated Protein Kinases