The GPER1 Agonist G-1 Attenuates Endothelial Cell Proliferation by Inhibiting DNA Synthesis and Accumulating Cells in the S and G2 Phases of the Cell Cycle
The GPER1 Agonist G-1 Attenuates Endothelial Cell Proliferation by Inhibiting DNA Synthesis and Accumulating Cells in the S and G2 Phases of the Cell Cycle
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DOI：
10.1159/000322578
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发表时间：
2011-01-01
影响因子：
1.7
通讯作者：
Nilsson, Bengt-Olof
中科院分区：
文献类型：
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作者：
Holm, Anders;Baldetorp, Bo;Nilsson, Bengt-Olof
G蛋白偶联受体30(GPR30)或G蛋白偶联雌激素受体1(GPER1)在血管中表达，但其在血管中的重要性尚不清楚。在这里，我们使用小鼠微血管内皮细胞bEnd.3细胞来研究GPER1激动剂G-1对内皮细胞增殖的影响。BEnd.3细胞表达GPER1的mRNA。BEnd.3细胞同时表达ERα和ERβ免疫反应。经G-1处理后，DNA合成减少，细胞数减少，IC50值约为2亩M。GPER1 siRNA可阻止G-1诱导的DNA合成减弱。G-1作用于细胞周期中的S和G2期细胞，提示G-1阻断了G2-M期的过渡，对仅弱表达GPER1mRNA的COS-7细胞的DNA合成没有影响。17β-雌二醇在生理浓度(NM)下对DNA合成无影响。内质网阻滞剂ICI182780减少DNA合成，效力与G-1相似。ERK/MAP激酶抑制剂PD98059对G-1诱导的DNA合成抑制无影响。G-1不仅能抑制bEnd.3细胞的增殖，还能抑制人脐静脉内皮细胞和HMEC-1内皮细胞的增殖。我们的结论是，GPER1激动剂G-1通过抑制DNA合成和通过在S和G2中积聚细胞来抑制内皮细胞的增殖。版权所有(C)2011 S.Karger AG，巴塞尔
G protein-coupled receptor 30 (GPR30) or G protein-coupled estrogen receptor 1 (GPER1) is expressed in the vasculature, but the importance of vascular GPER1 remains to be clarified. Here we investigate effects of the GPER1 agonist G-1 on endothelial cell proliferation using mouse microvascular endothelial bEnd.3 cells. The bEnd.3 cells express mRNA for GPER1. The bEnd.3 cells expressed both ER alpha and ER beta immunoreactivities. Treatment with G-1 reduced DNA synthesis and cell number with IC50 values of about 2 mu M. GPER1 siRNA prevented G-1-induced attenuation of DNA synthesis. G-1 accumulated cells in S and G2 phases of the cell cycle, suggesting that G-1 blocks transition between G2 and M. G-1 had no effect on DNA synthesis in COS-7 cells only weakly expressing GPER1 mRNA. 17 beta-Estradiol had no effect on DNA synthesis in physiological concentrations (nM). The ER blocker ICI182780 reduced DNA synthesis with similar potency as G-1. Treatment with the ERK/MAP kinase inhibitor PD98059 had no effect on G-1-induced attenuation of DNA synthesis. G-1-induced antiproliferation was observed not only in bEnd.3 cells but also in human umbilical vein endothelial cells and HMEC-1 endothelial cells. We conclude that the GPER1 agonist G-1 attenuates endothelial cell proliferation via inhibition of DNA synthesis and by accumulation of cells in S and G2. Copyright (C) 2011 S. Karger AG, Basel