• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>The journal of sexual medicine >Post-translational regulation of endothelial nitric oxide synthase (eNOS) by estrogens in the rat vagina.
【24h】

Post-translational regulation of endothelial nitric oxide synthase (eNOS) by estrogens in the rat vagina.

机译：大鼠阴道中的雌激素对内皮型一氧化氮合酶（eNOS）的翻译后调节。

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

INTRODUCTION: Estrogens control vaginal blood flow during female sexual arousal mostly through nitric oxide (NO). Although vascular effects of estrogens are attributed to an increase in endothelial NO production, the mechanisms of endothelial NO synthase (eNOS) regulation by estrogens in the vagina are largely unknown. AIMS: Our hypothesis was that estrogens regulate eNOS post-translationally in the vagina, providing a mechanism to affect NO bioavailability without changes in eNOS protein expression. METHODS: We measured eNOS phosphorylation and eNOS interaction with caveolin-1 and heat shock protein 90 (HSP90) in the distal and proximal vagina of female rats at diestrus, 7 days after ovariectomy and 2 days after replacement of ovariectomized rats with estradiol-17beta (15 microg). MAIN OUTCOME MEASURES: Molecular mechanisms of eNOS regulation by estrogen in the rat vagina. RESULTS: We localized phospho-eNOS (Ser-1177) immunohistochemically to the endothelium lining blood vessels and vaginal sinusoids. Estrogen withdrawal decreased phosphorylation of eNOS on its positive regulatory site (Ser-1177) and increased eNOS binding to its negative regulator caveolin-1 (without affecting eNOS/HSP90 interaction), and they were both normalized by estradiol replacement. Protein expressions of phosphorylated Akt (protein kinase B) and extracellular signal-regulated protein kinase 1/2 (ERK1/2) were not affected by estrogen status, suggesting that the effect of estrogens on eNOS (Ser-1177) phosphorylation was not mediated by activated AKT or ERK1/2. eNOS phosphorylation on its negative regulatory site (Ser-114) was increased in the vagina by estrogen withdrawal and normalized by estradiol replacement, implying that the maintenance of low phosphorylation of eNOS on this site by estradiol may limit eNOS interaction with caveolin-1 and preserve the enzyme's activity. Total eNOS, inducible NOS, caveolin-1, and HSP90 protein expressions were not affected by ovariectomy or estradiol replacement in the distal or proximal vagina. CONCLUSIONS: These results define novel estrogen signaling mechanisms in the vagina which involve eNOS phosphorylation and eNOS-caveolin-1 interaction.
机译：简介：雌激素在女性性唤起过程中主要通过一氧化氮（NO）控制阴道血流。尽管雌激素的血管作用归因于内皮一氧化氮产生的增加，但是在很大程度上，雌激素在阴道中调节内皮一氧化氮合酶（eNOS）的机制尚不清楚。目的：我们的假设是雌激素在阴道翻译后调节eNOS，提供了一种在不改变eNOS蛋白表达的情况下影响NO生物利用度的机制。方法：我们在雌性大鼠的雌性双侧睾丸，卵巢切除术后7天和卵巢切除大鼠用雌二醇17β替代后2天测量了eNOS磷酸化以及eNOS与小窝蛋白1和热休克蛋白90（HSP90）的相互作用。 15微克）。主要观察指标：雌激素在大鼠阴道内调节eNOS的分子机制。结果：我们免疫组织化学方法将磷酸化-eNOS（Ser-1177）定位于内皮细胞壁血管和阴道正弦曲线。雌激素戒断减少了其正调控位点（Ser-1177）上eNOS的磷酸化，并增强了eNOS与其负调控因子Caveolin-1的结合（不影响eNOS / HSP90相互作用），并且都通过雌二醇替代使其标准化。磷酸化的Akt（蛋白激酶B）和细胞外信号调节的蛋白激酶1/2（ERK1 / 2）的蛋白表达不受雌激素状态的影响，表明雌激素对eNOS（Ser-1177）磷酸化的影响不受激活AKT或ERK1 / 2。雌激素撤药可增加其阴性调节位点（Ser-114）上的eNOS磷酸化，并通过雌二醇替代使其正常化，这意味着雌二醇在该位点维持eNOS的低磷酸化可能会限制eNOS与小窝蛋白1的相互作用并保存酶的活性。阴道远端或近端卵巢切除术或雌二醇替代未影响总eNOS，诱导型NOS，caveolin-1和HSP90蛋白的表达。结论：这些结果确定了阴道中新的雌激素信号传导机制，涉及eNOS磷酸化和eNOS-caveolin-1相互作用。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号