Inhibitory effect of estrogen on Rac1-expression in monocytes.

Abstract

Recruitment of circulating monocytes into the vasculature and release of reactive oxygen species (ROS) promote atherogenesis. Rac1-GTPase is an essential component of the superoxide-producing NADPH-oxidase complex. Estrogens inhibit production of vascular reactive oxygen species. Angiotensin II as well as overexpression of the constitutively active mutant RacL61 increased ROS production in monocytes. AngII-mediated ROS release was completely inhibited by overexpression of the dominant negative mutant RacN17 or treatment with 17beta-estradiol. 17beta-Estradiol reduced Rac1-expression concentration- and time-dependently and decreased basal, as well as AngII-induced Rac1 activity. The effects of 17beta-estradiol were receptor-mediated. In vivo, down-regulation of Rac1 by 17beta-estradiol was observed in human mononuclear cells of women with elevated 17beta-estradiol levels after controlled ovarian hyperstimulation. In summary, the data show that down-regulation of Rac1-GTPase contributes to the inhibition of angiotensin II-mediated superoxide release by 17beta-estradiol in monocytes.

• Authors: Oliver Adam, Marion Hagel, Katharina Theobald, Michael Böhm, Ulrich Laufs
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 386 Issue 1 Pg. 45-9 (Aug 14 2009) ISSN: 1090-2104 [Electronic] United States
• PMID: 19497305 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Estrogens
• Reactive Oxygen Species
• Superoxides
• Angiotensin II
• Estradiol
• rac1 GTP-Binding Protein

Topics

• Angiotensin II (metabolism, pharmacology)
• Down-Regulation
• Estradiol (metabolism, pharmacology)
• Estrogens (metabolism, pharmacology)
• Gene Expression Regulation, Developmental
• Humans
• Monocytes (drug effects, enzymology)
• Reactive Oxygen Species (antagonists & inhibitors, metabolism)
• Superoxides (antagonists & inhibitors, metabolism)
• rac1 GTP-Binding Protein (antagonists & inhibitors, biosynthesis, genetics)