Thioredoxin Binding Protein-2 Regulates Autophagy of Human Lens Epithelial Cells under Oxidative Stress via Inhibition of Akt Phosphorylation.
Thioredoxin Binding Protein-2 Regulates Autophagy of Human Lens Epithelial Cells under Oxidative Stress via Inhibition of Akt Phosphorylation.
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硫氧还蛋白结合蛋白-2 通过抑制 Akt 磷酸化调节氧化应激下人晶状体上皮细胞的自噬
DOI：
10.1155/2016/4856431
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发表时间：
2016
影响因子：
--
通讯作者：
Yu Y
中科院分区：
文献类型：
--
作者：
Zhou J;Yao K;Zhang Y;Chen G;Lai K;Yin H;Yu Y
氧化应激在老年性白内障的发生发展中起重要作用。硫氧还蛋白结合蛋白-2(TBP-2)是硫氧还蛋白(Trx)的负性调节因子，可破坏细胞的抗氧化系统。本研究旨在探讨TBP-2在氧化应激条件下对人晶状体上皮细胞(LECs)自噬的调节作用。用人晶状体上皮细胞进行细胞培养和处理。采用慢病毒转染法实现TBP-2基因的高效表达。细胞毒性实验、Western印迹分析、GFP/mCherry融合的LC3质粒、免疫荧光和透射电子显微镜观察。结果表明，氧化应激可诱导LC_3-II、P_(62)和GFP/mCherry-LC_3点(P<；0.01)升高的LECs发生自噬反应。TBP-2的过表达进一步加强了这一反应，并使细胞活力恶化(P<；0.01)。TBP-2基因敲除可减轻氧化应激引起的自噬反应和细胞活力丧失。TBP-2主要调节起始阶段的自噬，这种自噬不依赖于mTOR，可能是由氧化应激下Akt的去磷酸化引起的。这些发现表明，TBP-2在氧化应激下的人晶状体上皮细胞中发挥了新的作用。氧化应激可导致晶状体上皮细胞损伤和自噬，TBP-2调节这一反应。因此，本研究为TBP-2在晶状体中的作用以及白内障发生的可能机制提供了证据。
Oxidative stress plays an essential role in the development of age-related cataract. Thioredoxin binding protein-2 (TBP-2) is a negative regulator of thioredoxin (Trx), which deteriorates cellular antioxidant system. Our study focused on the autophagy-regulating effect of TBP-2 under oxidative stress in human lens epithelial cells (LECs). Human lens epithelial cells were used for cell culture and treatment. Lentiviral-based transfection system was used for overexpression of TBP-2. Cytotoxicity assay, western blot analysis, GFP/mCherry-fused LC3 plasmid, immunofluorescence, and transmission electronic microscopy were performed. The results showed that autophagic response of LECs with increased LC3-II, p62, and GFP/mCherry-LC3 puncta (P < 0.01) was induced by oxidative stress. Overexpression of TBP-2 further strengthens this response and worsens the cell viability (P < 0.01). Knockdown of TBP-2 attenuates the autophagic response and cell viability loss induced by oxidative stress. TBP-2 mainly regulates autophagy in the initiation stage, which is mTOR-independent and probably caused by the dephosphorylation of Akt under oxidative stress. These findings suggest a novel role of TBP-2 in human LECs under oxidative stress. Oxidative stress can cause cell injury and autophagy in LECs, and TBP-2 regulates this response. Hence, this study provides evidence regarding the role of TBP-2 in lens and the possible mechanism of cataract development.
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影响因子：
4.8
作者：
Hong, Shin Yee;Yu, Fa-Xing;Hagen, Thilo
通讯作者：
Hagen, Thilo
影响因子：
4
作者：
Lichtenstein, Alexandra;Minogue, Peter J.;Berthoud, Viviana M.
通讯作者：
Berthoud, Viviana M.
DOI：
10.1083/jcb.200412022
发表时间：
2005-05-09
期刊：
The Journal of cell biology
影响因子：
--
作者：
Komatsu M;Waguri S;Ueno T;Iwata J;Murata S;Tanida I;Ezaki J;Mizushima N;Ohsumi Y;Uchiyama Y;Kominami E;Tanaka K;Chiba T
通讯作者：
Chiba T
影响因子：
21.3
作者：
Komatsu, Masaaki;Kurokawa, Hirofumi;Yamamoto, Masayuki
通讯作者：
Yamamoto, Masayuki
影响因子：
13.3
作者：
Lin WJ;Kuang HY
通讯作者：
Kuang HY