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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.

Holm, Anders LU ; Baldetorp, Bo LU ; Olde, Björn LU ; Leeb-Lundberg, Fredrik LU and Nilsson, Bengt-Olof LU (2011) In Journal of Vascular Research 48(4). p.327-335
Abstract
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... (More)
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. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of Vascular Research
volume
48
issue
4
pages
327 - 335
publisher
Karger
external identifiers
  • wos:000291752700006
  • pmid:21273787
  • scopus:79151480468
ISSN
1423-0135
DOI
10.1159/000322578
language
English
LU publication?
yes
id
7faa2349-a317-4a2d-b2ea-78f0df0f504d (old id 1777015)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/21273787?dopt=Abstract
date added to LUP
2011-02-01 09:26:19
date last changed
2017-04-23 04:40:58
@article{7faa2349-a317-4a2d-b2ea-78f0df0f504d,
  abstract     = {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.},
  author       = {Holm, Anders and Baldetorp, Bo and Olde, Björn and Leeb-Lundberg, Fredrik and Nilsson, Bengt-Olof},
  issn         = {1423-0135},
  language     = {eng},
  number       = {4},
  pages        = {327--335},
  publisher    = {Karger},
  series       = {Journal of Vascular Research},
  title        = {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.},
  url          = {http://dx.doi.org/10.1159/000322578},
  volume       = {48},
  year         = {2011},
}