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首页> 外文期刊>Cellular Physiology and Biochemistry >Gender differences in serum and glucocorticoid regulated kinase-1 (SGK-1) expression during renal ischemia/reperfusion injury
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Gender differences in serum and glucocorticoid regulated kinase-1 (SGK-1) expression during renal ischemia/reperfusion injury

机译:肾脏缺血/再灌注损伤期间血清和糖皮质激素调节激酶-1(SGK-1)表达的性别差异

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摘要

Several studies reported sexual dimorphism in the signaling mechanisms of renal ischemia/reperfusion (I/R). The anti-apoptotic serum and glucocorticoid-regulated kinase-1 (SGK-1) is up-regulated and has a significant protective role in renal I/R. SGK-1 has several target molecules, and inhibition of the inducible nitric oxide synthase (iNOS) transcription is one of its effector mechanisms. The objective of the present study was to examine if there is a gender-specific expression and activation of SGK-1 during renal I/R injury. In vitro, treatment of HK-2 kidney proximal tubular cells with different concentrations of 17-beta estradiol had no effect, whereas testosterone increased SGK-1 abundance in a dose-dependent manner. In vivo, in a rat model of unilateral renal I/R injury, there was a higher SGK-1 expression and phosphorylation in males 2 and 24 h after ischemia paralleled by reduction in the mRNA expression of iNOS compared to females. Deprivation of testosterone by castration of males resulted in decreased SGK-1 protein level at all time-points and reduced phosphorylation 2 and 24 h after reperfusion. Our results suggest that testosterone up-regulates SGK-1 in the kidney contributing to sexual dimorphisms in the cell signalling machinery. The significance of the testosterone-regulated SGK-1 level and activity in the kidney needs further investigations.
机译:几项研究报道了肾脏缺血/再灌注(I / R)信号传导机制中的性二态性。抗凋亡血清和糖皮质激素调节激酶-1(SGK-1)上调,在肾脏I / R中具有重要的保护作用。 SGK-1具有多个靶分子,抑制诱导型一氧化氮合酶(iNOS)转录是其效应器机制之一。本研究的目的是检查肾I / R损伤期间是否存在性别特异性表达和SGK-1的激活。在体外,用不同浓度的17-β雌二醇治疗HK-2肾近端肾小管细胞无效,而睾丸激素以剂量依赖性方式增加SGK-1的丰度。在体内,在单侧肾I / R损伤的大鼠模型中,缺血后2小时和24小时,雄性中SGK-1的表达和磷酸化更高,与雌性相比,iNOS的mRNA表达降低。雄性cast割剥夺睾丸激素可导致在所有时间点SGK-1蛋白水平降低,再灌注后2和24 h磷酸化降低。我们的结果表明,睾丸激素上调肾脏中的SGK-1,从而导致细胞信号传导机制中的性二态性。肾脏中睾酮调节的SGK-1水平和活性的意义需要进一步研究。

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