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.
Author
Summary, in English
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 ERα and ERβ immunoreactivities. Treatment with G-1 reduced DNA synthesis and cell number with IC(50) values of about 2 μM. 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. 17β-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.
Department/s
- Vascular Physiology
- Breastcancer-genetics
- Drug Target Discovery
- Cardiology
Publishing year
2011
Language
English
Pages
327-335
Publication/Series
Journal of Vascular Research
Volume
48
Issue
4
Full text
Links
Document type
Journal article
Publisher
Karger
Topic
- Cardiac and Cardiovascular Systems
Status
Published
Research group
- Vascular Physiology
- Drug Target Discovery
ISBN/ISSN/Other
- ISSN: 1423-0135