Quercetin Inhibits AQP1 Translocation in High-Glucose-Cultured SRA01/04 Cells Through PI3K/Akt/mTOR Pathway

Objective: The study aimed to investigate the effects of quercetin on Aquaporin 1 (AQP1) translocation in high glucose condition and made an attempt to clarify the underlying mechanisms and provide new ideas for the treatment of diabetic cataract (DC). Methods: The human lens epithelial line SRA01/04 cells were divided into groups mentioned be-low: normal glucose, high glucose with a specific time (0 h, 2 h, 4 h, 8 h, 12 h, 24 h), high glucose plus the phosphoinositide 3-kinase (PI3K) inhibitor LY294002, high glucose plus the mammalian target of rapamycin (mTOR) inhibitor rapamycin, and high glucose plus quercetin with different doses (2 mu mol/L, 4 mu mol/L and 8 mu mol/L). The western blotting assay was used to detect the pro-tein kinase B (Akt), phosphorylated protein kinase B (p-Akt), mammalian target of rapamycin (m -TOR), phosphorylated mammalian target of rapamycin (p-mTOR) and AQP1. Real-time poly-merase chain reaction (RT-PCR) was used to detect the expression of AQP1. A Membrane and Cy-tosol Protein Extraction Kit was applied to separate membrane proteins. Immunofluorescence as-say was performed to evaluate the expression and location of AQP1. The effect of quercetin on the expression of AQP1 and PI3K/Akt/mTOR signaling was detected. Results: AQP1 protein was found to be significantly increased in 24 hour when exposed to high glucose condition (P<0.01). LY294002 and rapamycin inhibited PI3K/Akt/mTOR and AQP1 ex -pression (P<0.01), preventing the change of AQP1 location in the SRA01/04 plasma membrane (P<0.01). This effect was further proved by immunofluorescence. In different doses of quercetin groups (2 mu mol/L, 4 mu mol/L and 8 mu mol/L), the phosphorylation of mTOR and Akt were decreased and AQP1 in the membrane was changed compared with high glucose group (P<0.01). Conclusion: Quercetin significantly decreased the AQP1 elevation and prevented the change of AQP1 location through inhibiting the activation of the PI3K/Akt/mTOR signaling in high-glucose--cultured SRA01/04 cells, which might have the preventable and inhibitory effects on the early de-velopment of diabetic cataract. The specific pathophysiological role of quercetin still needs to be verified.