Rusai Krisztina, Wagner Bettina, Roos Marcel, Schmaderer Christoph, Strobl Matthias, Boini Krishna M, Grenz Almut, Kuhl Dietmar, Heemann Uwe, Lang Florian, Lutz Jens
First Department of Pediatrics, Semmelweis University, Budapest, Hungary.
Cell Physiol Biochem. 2009;24(5-6):577-84. doi: 10.1159/000257527. Epub 2009 Nov 4.
The serum- and glucocorticoid-inducible kinase 1 (SGK1) is a serine threonine protein kinase activated through the phosphatidylinositol 3-kinase (PI3-kinase) pathway and counteracting apoptosis. Protein expression and activation of SGK1 are increased in various models of cell stress. The present study explored the role of SGK1 in renal hypoxia/ischemia induced apoptosis. HEK 293 cells were exposed in vitro to hypoxia/reoxygenation (H/R), which increased SGK1 transcript levels, SGK1 protein abundance and SGK1 phosphorylation. H/R injury further enhanced the percentage of apoptotic cells, an effect significantly blunted by prior SGK1 overexpression. In vivo renal ischemia/reperfusion (I/R) injury increased SGK1 transcript levels and SGK1 protein abundance. I/R enhanced apoptosis, an effect significantly more pronounced in gene targeted mice lacking SGK1. In conclusion, SGK1 is up-regulated and counteracts apoptosis following H/R in vitro and ischemia In vivo.
血清和糖皮质激素诱导激酶1（SGK1）是一种丝氨酸苏氨酸蛋白激酶，通过磷脂酰肌醇3激酶（PI3激酶）途径激活，并对抗细胞凋亡。在各种细胞应激模型中，SGK1的蛋白表达和活性都会增加。本研究探讨了SGK1在肾缺氧/缺血诱导的细胞凋亡中的作用。体外将人胚肾293细胞（HEK 293细胞）暴露于缺氧/复氧（H/R）环境中，这会增加SGK1转录水平、SGK1蛋白丰度和SGK1磷酸化水平。H/R损伤进一步增加了凋亡细胞的百分比，而预先过表达SGK1可显著减弱这一效应。在体内，肾缺血/再灌注（I/R）损伤会增加SGK1转录水平和SGK1蛋白丰度。I/R增强了细胞凋亡效应，在缺乏SGK1的基因靶向小鼠中这种效应更为明显。总之，在体外H/R和体内缺血后，SGK1上调并对抗细胞凋亡。
