title: Thioredoxin Binding Protein-2 Regulates Autophagy of Human Lens Epithelial Cells under Oxidative Stress via Inhibition of Akt Phosphorylation.
abstract: 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.
authors.affiliation: Eye Center, 2nd Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China; Department of Otolaryngology, 2nd Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.
authors.forename: Jiaojie
authors.identifier: 0000-0002-5050-3576
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Eye Center, 2nd Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.
authors.forename: Ke
authors.initials: K
authors.lastname: Yao
authors.affiliation: Eye Center, 2nd Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.
authors.forename: Yidong
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Public Health, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.
authors.forename: Guangdi
authors.initials: G
authors.lastname: Chen
authors.affiliation: Eye Center, 2nd Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.
authors.forename: Kairan
authors.initials: K
authors.lastname: Lai
authors.affiliation: Eye Center, 2nd Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.
authors.forename: Houfa
authors.initials: H
authors.lastname: Yin
authors.affiliation: Eye Center, 2nd Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.
authors.forename: Yibo
authors.identifier: 0000-0001-9256-4687
authors.initials: Y
authors.lastname: Yu