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线粒体未折叠蛋白反应基因CLPP改变线粒体动力学并影响线粒体功能。

Mitochondrial unfolded protein response gene CLPP changes mitochondrial dynamics and affects mitochondrial function.

作者信息

Wu GuiJun, Xiong Qing, Wei XiaoJun, Wang Ye, Hu XueMei, He GuangZhen, Liu LinJie, Lai QianHui, Dai Zhe, Anushesh Dhakal, Xu Yancheng

机构信息

Department of Endocrinology, Zhongnan Hospital of Wuhan University, Wuhan, China.

Emergency Centre, Zhongnan Hospital of Wuhan University, Wuhan, China.

出版信息

PeerJ. 2019 Jul 2;7:e7209. doi: 10.7717/peerj.7209. eCollection 2019.

Abstract

Mitochondrial dynamics is associated with mitochondrial function, which is associated with diabetes. Although an important indicator of the mitochondrial unfolded protein response, to the best of our knowledge, and its effects on mitochondrial dynamics in islet cells have not been studied to date. We analyzed the effects of on mitochondrial dynamics and mitochondrial function in the mice islet β-cell line Min6 under high glucose and high fat conditions. Min6 cells were assigned to: Normal, HG, HG+NC, HG+si, HF, HF+NC and HF+ si groups. High glucose and high fat can promote the mRNA and protein expression of in mitochondria. The increase of mitochondrial fission, the decrese of mitochondrial fusion, and the damage of mintocondrial ultrastructure were significant in the si cell groups as compared to no-si treated groups. Meanwhile, mitochondrial functions of MIN6 cells treated with si were impaired, such as ATP decreased, ROS increased, mitochondrial membrane potential decreased. In addition, cell insulin secretion decreased and cell apoptosis rate increased in si groups. These results revealed that mitochondrial unfolded protein response gene alleviated high glucose and high fat-induced mitochondrial dynamics imbalance and mitochondrial dysfunction.

摘要

线粒体动力学与线粒体功能相关,而线粒体功能又与糖尿病相关。尽管线粒体未折叠蛋白反应是一个重要指标,但据我们所知,其对胰岛细胞中线粒体动力学的影响迄今为止尚未得到研究。我们分析了在高糖和高脂条件下,[未提及的物质]对小鼠胰岛β细胞系Min6中线粒体动力学和线粒体功能的影响。Min6细胞被分为:正常组、高糖组、高糖+阴性对照组、高糖+干扰组、高脂组、高脂+阴性对照组和高脂+干扰组。高糖和高脂可促进线粒体中[未提及的物质]的mRNA和蛋白表达。与未进行干扰处理的组相比,干扰细胞组中线粒体分裂增加、线粒体融合减少以及线粒体超微结构损伤显著。同时,用干扰处理的MIN6细胞的线粒体功能受损,如ATP减少、活性氧增加、线粒体膜电位降低。此外,干扰组中细胞胰岛素分泌减少且细胞凋亡率增加。这些结果表明,线粒体未折叠蛋白反应基因减轻了高糖和高脂诱导的线粒体动力学失衡和线粒体功能障碍。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cb98/6611452/d138c315ba1f/peerj-07-7209-g001.jpg

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