Mitochondrial Uncoupling Protein 2 in human cumulus cells is associated with regulating autophagy and apoptosis, maintaining gap junction integrity and progesterone synthesis
Mitochondrial Uncoupling Protein 2 in human cumulus cells is associated with regulating autophagy and apoptosis, maintaining gap junction integrity and progesterone synthesis
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人卵丘细胞中的线粒体解偶联蛋白 2 与调节自噬和细胞凋亡、维持间隙连接完整性和孕酮合成有关
DOI：
10.1016/j.mce.2017.01.020
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发表时间：
2017-03-05
影响因子：
4.1
通讯作者：
Lin, Zhenkun
中科院分区：
文献类型：
--
作者：
Ge, Hongshan;Zhang, Fan;Lin, Zhenkun
为探讨线粒体解偶联蛋白2（UCP 2）在卵丘细胞（CC）中的作用，体外培养人CC，用特异性UCP 2抑制剂京尼平（Genipin）或RNA干扰技术抑制UCP 2表达。UCP 2抑制后，三磷酸腺苷水平和ADP/ATP比值无显著差异。UCP 2抑制导致细胞氧化损伤显著增加，这反映在几个关键参数的改变中，包括活性氧（ROS）和脂质过氧化水平以及还原型GSH与GSSG的比率。阻断UCP 2后，Caspase-3活性明显增加，同时Caspase-3活性下降，LC 3-II/LC 3-I比值显著升高，提示UCP 2抑制可引起细胞凋亡和自噬。缝隙连接蛋白43（Cx43）的mRNA和蛋白表达在京尼平或siRNA处理后显著降低。在UCP 2抑制后，培养基中的孕酮水平也显著降低。UCP 2在调控ROS产生、细胞凋亡和自噬、维持间隙连接完整性和孕酮合成等方面发挥重要作用，提示UCP 2参与卵泡发育和早期胚胎着床的调控，可能是卵母细胞质量和能力的潜在生物标志物。(C)2017爱思唯尔B. V.保留所有权利。
To explore the roles of mitochondrial Uncoupling Protein 2 (UCP2) in cumulus cells (CCs), human CCs were cultured in vitro, and the UCP2 was inhibited by treatment with Genipin, a special UCP inhibitor, or by RNA interference targeting UCP2. No significant differences in adenosine triphosphate levels and the ratio of ADP/ATP were observed after UCP2 inhibition. UCP2 inhibition caused a significant increase in cellular oxidative damage, which was reflected in alterations to several key parameters, including reactive oxygen species (ROS) and lipid peroxidation levels and the ratio of reduced GSH to GSSG. UCP2 blocking resulted in an obvious increase in active Caspase-3, accompanied by the decline of proactive Caspase-3 and a significant increase in the LC3-II/LC3-I ratio, suggesting that UCP2 inhibition triggered cellular apoptosis and autophagy. The mRNA and protein expression of connexin 43 (Cx43), a gap junction channel protein, were significantly reduced after treatment with Genipin or siRNA. The progesterone level in the culture medium was also significantly decreased after UCP2 inhibition. Our data indicated that UCP2 plays highly important roles in mediating ROS production and regulating apoptosis and autophagy, as well as maintaining gap junction integrity and progesterone synthesis, which suggests that UCP2 is involved in the regulation of follicle development and early embryo implantation and implies that it might serve as a potential biomarker for oocyte quality and competency. (C) 2017 Elsevier B.V. All rights reserved.