The G protein-coupled oestrogen receptor 1 agonist G-1 disrupts endothelial cell microtubule structure in a receptor-independent manner

Anders Holm, Per Olof Grände, Richard F. Ludueña, Björn Olde, Veena Prasad, L. M Fredrik Leeb-Lundberg, Bengt Olof Nilsson

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

The G protein-coupled oestrogen receptor GPER1, also known as GPR30, has been implicated in oestrogen signalling, but the physiological importance of GPER1 is not fully understood. The GPER1 agonist G-1 has become an important tool to assess GPER1-mediated cellular effects. Here, we report that this substance, besides acting via GPER1, affects the microtubule network in endothelial cells. Treatment with G-1 (3 μM) for 24 h reduced DNA synthesis by about 60 % in mouse microvascular endothelial bEnd.3 cells. Treatment with 3 μM G-1 prevented outgrowth of primary endothelial cells from mouse aortic explants embedded in Matrigel. Treatment with G-1 (0.3-3 μM) for 24 h disrupted bEnd.3 cell and HUVEC microtubule structure in a concentration- dependent manner as assessed by laser-scanning confocal immunofluorescence microscopy. G-1-induced (3 μM) disruption of microtubule was observed also after acute (3 and 6 h) treatment and in the presence of the protein synthesis inhibitor cycloheximide. Disruption of microtubules by 3 μM G-1 was observed in aortic smooth muscle cells obtained from both GPER1 knockout and wild-type mice, suggesting that G-1 influences microtubules through a mechanism independent of GPER1. G-1 dose dependently (10-50 μM) stimulated microtubule assembly in vitro. On the other hand, microtubules appeared normal in the presence of 10-50 μM G-1 as determined by electron microscopy. We suggest that G-1-promoted endothelial cell anti-proliferation is due in part to alteration of microtubule organization through a mechanism independent of GPER1. This G-1-promoted mechanism may be used to block unwanted endothelial cell proliferation and angiogenesis such as that observed in, e.g. cancer.

Original languageEnglish (US)
Pages (from-to)239-249
Number of pages11
JournalMolecular and Cellular Biochemistry
Volume366
Issue number1-2
DOIs
StatePublished - Jul 2012

Fingerprint

Estrogen Receptor alpha
Endothelial cells
G-Protein-Coupled Receptors
GTP-Binding Proteins
Microtubules
Estrogens
Endothelial Cells
Protein Synthesis Inhibitors
Confocal microscopy
Cell proliferation
Cycloheximide
Estrogen Receptors
Electron microscopy
Muscle
Cells
Cell Proliferation
Scanning
Lasers
DNA
Human Umbilical Vein Endothelial Cells

Keywords

  • Endothelial cells
  • G-1
  • GPR30
  • Microtubule
  • Proliferation
  • Tubulin

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

The G protein-coupled oestrogen receptor 1 agonist G-1 disrupts endothelial cell microtubule structure in a receptor-independent manner. / Holm, Anders; Grände, Per Olof; Ludueña, Richard F.; Olde, Björn; Prasad, Veena; Leeb-Lundberg, L. M Fredrik; Nilsson, Bengt Olof.

In: Molecular and Cellular Biochemistry, Vol. 366, No. 1-2, 07.2012, p. 239-249.

Research output: Contribution to journalArticle

Holm, Anders ; Grände, Per Olof ; Ludueña, Richard F. ; Olde, Björn ; Prasad, Veena ; Leeb-Lundberg, L. M Fredrik ; Nilsson, Bengt Olof. / The G protein-coupled oestrogen receptor 1 agonist G-1 disrupts endothelial cell microtubule structure in a receptor-independent manner. In: Molecular and Cellular Biochemistry. 2012 ; Vol. 366, No. 1-2. pp. 239-249.
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