Involvement of hypoxia-inducible factor-1α in the oxidative stress induced by advanced glycation end products in murine Leydig cells
Involvement of hypoxia-inducible factor-1α in the oxidative stress induced by advanced glycation end products in murine Leydig cells
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DOI：
10.1016/j.tiv.2015.12.016
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发表时间：
2016-04-01
影响因子：
3.2
通讯作者：
Sun, Daguang
中科院分区：
文献类型：
--
作者：
Chen, Ying;Zhang, Yi;Sun, Daguang
高血压增加晚期糖基化终产物（AGEs）的形成，触发氧化损伤，影响诱导因子（HIF）-1 α蛋白水平和反式激活功能。睾丸中的HIF-1 α受损导致男性不育。本研究的目的是研究HIF-1 α在AGES诱导的小鼠Leydig TM 3细胞氧化应激中的作用。TM 3细胞分别用50 μ g/ml AGEs或HIF-1 α siRNA或500 μ M DMOG（二甲基草酰甘氨酸）处理。还用HIF-1 α siRNA或500 μ M DMOG预处理细胞，然后用50 μ g/ml AGEs处理。检测细胞内活性氧（ROS）的生成及细胞凋亡情况。Western blotting检测caspase-3、血红素加氧酶（HO）-1、类固醇生成急性调节蛋白（星星）和细胞色素P450 17 α多肽1（CYP 17 A1）的表达。AGEs可增加TM 3细胞ROS的产生，诱导细胞凋亡，并激活HIF-1 α和HO-1。HIF-1 α通过上调caspase-3的表达，减弱了AGE诱导的ROS形成，促进了细胞凋亡。HIF-1 α的敲低抑制了CYP 17 A1和星星的表达，并增强了AGEs对星星和CYP 17 A1的抑制作用。这些结果表明，减弱HIF-1 α加剧了小鼠Leydig细胞中AGEs的氧化应激损伤，并导致糖尿病男性不育。(C)2015爱思唯尔有限公司版权所有。
Hyperglycemia increases the formation of advanced glycation end products (AGEs), triggers oxidative impairments and influences inducible factor (HIF)-1 alpha protein levels and transactivation function. Compromised HIF-1 alpha in testis leads to male infertility. The aim of the study was to investigate the role of HIF-1 alpha in oxidative stress induced by AGES in murine Leydig TM3 cells. TM3 cells were treated with 50 mu g/ml of AGEs, or HIF-1 alpha siRNA or 500 mu M of DMOG (dimethyloxalylglycine) respectively. The cells were also pretreated with HIF-1 alpha siRNA or 500 mu M of DMOG and then were treated with 50 mu g/ml of AGEs. The formation of reactive oxygen species (ROS) and cell apoptosis was evaluated. The expression of caspase-3, Heme oxygenase (HO)-1, steroidogenic acute regulatory protein (StAR) and cytochrome P450 17 alpha polypeptide 1 (CYP17A1) was examined by Western blotting. AGEs increased ROS production, induced apoptosis and activated HIF-1 alpha and HO-1 in TM3 cells. HIF-1 alpha attenuated the AGE-induced ROS formation and promoted apoptosis via the upregulation of caspase-3. Knockdown of HIF-1 alpha inhibited the expression of CYP17A1 and StAR, and enhanced the inhibition of StAR and CYP17A1 by AGEs. These findings indicate that attenuated HIF-1 alpha exacerbates the oxidative stress injury by AGEs in murine Leydig cells, and contributes to diabetic male infertility. (C) 2015 Elsevier Ltd. All rights reserved.