Thioredoxin Binding Protein-2 Regulates Autophagy of Human Lens Epithelial Cells under Oxidative Stress via Inhibition of Akt Phosphorylation

Abstract EN

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.