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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/1777015
- author
- Holm, Anders
LU
; Baldetorp, Bo
LU
; Olde, Björn
LU
; Leeb-Lundberg, Fredrik
LU
and Nilsson, Bengt-Olof
LU
- organization
- publishing date
- 2011
- 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
- pmid:21273787
- 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
- 2016-04-04 09:45:39
- date last changed
- 2022-03-23 07:08:13
@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 = {{https://lup.lub.lu.se/search/files/5410195/1787816.pdf}},
doi = {{10.1159/000322578}},
volume = {{48}},
year = {{2011}},
}