Cyclosporin A inhibits mitochondrial biogenesis in Hep G2 cells
Cyclosporin A inhibits mitochondrial biogenesis in Hep G2 cells
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DOI：
10.1016/j.bbrc.2018.01.113
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发表时间：
2018-02-12
影响因子：
3.1
通讯作者：
Wu, Zhongjun
中科院分区：
文献类型：
--
作者：
Qi, Rui;Wang, Dongtao;Wu, Zhongjun
线粒体生物合成的失调与许多疾病的发病机制有关，包括肝脏疾病。环孢霉素A（CsA）是治疗自身免疫性疾病和预防器官移植排斥反应的常用药物之一，但已发现CsA可引起线粒体功能障碍。然而，CsA对线粒体功能障碍的细胞机制目前尚未完全阐明。在这项研究中，我们发现CsA在mRNA和蛋白水平上降低HepG 2细胞中PGC-1 α的表达。相应地，CsA处理后其靶基因NRF 1和TFAM的表达降低.此外，线粒体DN/nDNA，线粒体的质量，ATP的生产，和细胞色素C氧化酶活性显着降低与CsA治疗。发现PGC-1 α的过表达挽救了CsA给药对线粒体生物合成的负面影响。机制上，CREB参与CsA对线粒体生物合成的抑制作用。(C)2018由Elsevier Inc.出版
Dysregulation of mitochondrial biogenesis is associated with pathogenesis in many diseases, including liver diseases. Cyclosporine A (CsA), one of the most commonly used drug to treat many autoimmune diseases and to prevent allograft rejection after organ transplantation, has been reported to cause mitochondrial dysfunction. However, the cellular mechanisms underlying CsA on mitochondrial dysfunction remain at present not completely elucidated. In this study, we found that CsA reduced the expression of PGC-1 alpha at both the mRNA and protein levels in HepG2 cells. Correspondingly, the expressions of its target genes NRF 1 and TFAM were reduced in response to CsA treatment. In addition, mtDN/nDNA, mitochondria mass, ATP production, and cytochrome C oxidase activity were significantly reduced by treatment with CsA. Over-expression of PGC-1 alpha was found to rescue the negative effect of CsA administration on mitochondria] biogenesis. Mechanistically, CREB was involved in the inhibitory effects of CsA in mitochondrial biogenesis. (C) 2018 Published by Elsevier Inc.