Inhibitory effect of estrogen on Rac1-expression in monocytes
Inhibitory effect of estrogen on Rac1-expression in monocytes
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DOI：
10.1016/j.bbrc.2009.05.126
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发表时间：
2009-08-14
影响因子：
3.1
通讯作者：
Laufs, Ulrich
中科院分区：
文献类型：
--
作者：
Adam, Oliver;Hagel, Marion;Laufs, Ulrich
循环单核细胞募集到脉管系统中和活性氧 (ROS) 的释放促进动脉粥样硬化形成。 Rac1-GTPase 是产生超氧化物的 NADPH-氧化酶复合物的重要组成部分。雌激素抑制血管活性氧的产生。血管紧张素 II 以及组成型活性突变体 RacL61 的过度表达增加了单核细胞中 ROS 的产生。显性失活突变体 RacN17 的过表达或用 17β-雌二醇处理可完全抑制 AngII 介导的 ROS 释放。 17β-雌二醇可降低 Rac1 表达浓度和时间依赖性，并降低基础活性和 AngII 诱导的 Rac1 活性。 17β-雌二醇的作用是受体介导的。在体内，在受控卵巢过度刺激后，17β-雌二醇水平升高的女性的人单核细胞中观察到了 17β-雌二醇对 Rac1 的下调。 总之，数据表明，Rac1-GTPase 的小丑调节有助于抑制单核细胞中 17β-雌二醇介导的血管紧张素 II 介导的超氧化物释放。 (C) 2009 Elsevier Inc. 保留所有权利。
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 17 beta-estradiol. 17 beta-Estradiol reduced Rac1-expression concentration- and time-dependently and decreased basal, as well as AngII-induced Rac1 activity. The effects of 17 beta-estradiol were receptor-mediated. In vivo, down-regulation of Rac1 by 17 beta-estradiol was observed in human mononuclear cells of women with elevated 17 beta-estradiol levels after controlled ovarian hyperstimulation.In summary, the data show that clown-regulation of Rac1-GTPase contributes to the inhibition of angiotensin II-mediated superoxide release by 17 beta-estradiol in monocytes. (C) 2009 Elsevier Inc. All rights reserved.