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ABBS: mTOR mediates QDPR-induced autophagy

已有 1645 次阅读 2019-3-15 09:49 |个人分类:期刊新闻|系统分类:论文交流| mTOR, oxidative stress, kidney, autophagy

A278C mutation of dihydropteridine reductase decreases autophagy via mTOR signaling

Qin Si, Sifan Sun, and Yanting Gu

Aviation General Hospital of China Medical University, Beijing 100012, China

Acta Biochim Biophys Sin 2017, 49: 706–712; doi: 10.1093/abbs/gmx061

Dihydropteridine reductase (QDPR) plays an important role in the recycling of BH4 and is closely related to oxidative stress. We have previously reported that the overexpression of QDPR in human kidney HEK293T cells significantly protected against oxidative stress, and these beneficial effects were abolished by A278C mutation. To evaluate the effect of wild-type and mutant QDPR on autophagy and its mechanism in HEK293T cells, we constructed the wild-type and mutant QDPR expression plasmids and transfected them into HEK293T cells. Three days later, cells were collected to observe the expression of fusion protein and the intracellular production of reactive oxygen species (ROS). Western blot analysis was employed to evaluate the change of mTOR and ribosomal protein S6 kinase B1 (S6K1) signaling and the expression of LC-I, LC-II, Bcl-1, Bcl-2, p62, and p53. The results showed that the exogenous wild-type QDPR significantly decreased the expression of mTOR and phosphorylation of the mTOR and S6K1. Mutation of QDPR inhibited the regulation of mTOR, suggesting that QDPR is a positive regulator of autophagy via suppressing mTOR signaling. The expressions of p62, LC3-II and Beclin 1 were dramatically enhanced in wild-type QDPR group, which were reversed after QDPR mutation. Additionally, mutation of QDPR altered the upregulation of QDPR on Beclin 2. It is therefore concluded that QDPR appears to play an important role in enhancing autophagy, and its mutation contributes to dysregulation of autophagy.

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Inhibition of mTOR and upregulation of p62 by wild-type QDPR overexpression

阅读原文: http://www.abbs.org.cn/arts.asp?id=4188

获取全文: abbs@sibs.ac.cn

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