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The GPER Agonist G-1 Induces Mitotic Arrest and Apoptosis in Human Vascular Smooth Muscle Cells Independent of GPER.
- Source :
-
Journal of Cellular Physiology . Apr2015, Vol. 230 Issue 4, p885-895. 11p. - Publication Year :
- 2015
-
Abstract
- The G protein-coupled estrogen receptor (GPER) has been implicated in the regulation of smooth muscle cell (SMC) proliferation. The GPER selective agonist G-1 has been a useful tool for exploring the biological roles of GPER in a variety of experimental settings, including SMC proliferation. The present study, originally designed to investigate cellular and signaling mechanisms underlying the regulatory role of GPER in vascular SMC proliferation using G-1, unexpectedly revealed off-target effects of G-1. G-1(1-10 μM) inhibited bromodeoxyuridine (BrdU) incorporation of human SMCs and caused G2/M cell accumulation. G-1 treatment also increased mitotic index concurrent with a decrease in phosphorylation of Cdk1 (Tyr 15) and an increase in phosphorylation of the mitotic checkpoint protein BuBR1. Furthermore, G-1 caused microtubule disruption, mitotic spindle damage, and tubulin depolymerization. G-1 induced cell apoptosis as indicated by the appearance of TUNEL-positive and annexin V-positive cells with enhanced cleavage of caspases 3 and 9. However, neither the GPER antagonist G-15 nor the MAPK kinase inhibitor PD98059 prevented these G-1 effects. Down-regulation of GPER or p44/42 MAPK with siRNA transfection also did not affect the G-1-induced apoptosis. We conclude that G-1 inhibits proliferation of SMCs through mechanisms involving mitotic arrest and apoptosis, independent of GPER and the MAPK pathway. J. Cell. Physiol. 230: 885-895, 2015. © 2014 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 00219541
- Volume :
- 230
- Issue :
- 4
- Database :
- Academic Search Index
- Journal :
- Journal of Cellular Physiology
- Publication Type :
- Academic Journal
- Accession number :
- 100145316
- Full Text :
- https://doi.org/10.1002/jcp.24817