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.
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.
Authors: Sergi Clotet; Maria Jose Soler; Marta Riera; Julio Pascual; Fei Fang; Joyce Zhou; Ihor Batruch; Stella K Vasiliou; Apostolos Dimitromanolakis; Clara Barrios; Eleftherios P Diamandis; James W Scholey; Ana Konvalinka Journal: Mol Cell Proteomics Date: 2017-01-04 Impact factor: 5.911