Downregulation of AMPK dependent FOXO3 and TFEB involves in the inhibition of autophagy in diabetic cataract
| Autor: | Jiani Li, Qihang Sun, Xiaozhang Qiu, Jiaqing Zhang, Yuxing Zheng, Lixia Luo, Xuhua Tan |
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| Rok vydání: | 2021 |
| Předmět: |
Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
TOR Serine-Threonine Kinases Forkhead Box Protein O3 Down-Regulation AMP-Activated Protein Kinases Sensory Systems Cataract Cellular and Molecular Neuroscience Ophthalmology Glucose Autophagy Diabetes Mellitus Humans Beclin-1 Proto-Oncogene Proteins c-akt Signal Transduction |
| Zdroj: | Current eye research. 47(4) |
| ISSN: | 1460-2202 |
| Popis: | Autophagy plays a crucial role in intracellular quality control of crystalline lens and AMPK has regulatory effect on autophagy. However, whether AMPK regulated autophagy is involved in diabetic cataract (DC) progression remains unknown. This study aims to investigate the AMPK-FOXO3 and AMPK-TFEB induced autophagy activity in DC patients.First, anterior capsule specimens from DC and age-related cataract (ARC) patients were obtained to compare the expression difference of autophagy-related genes. The phosphorylation levels of AMPK, AKT, and mTOR and the expression of FOXO3 and TFEB were measured. Then, human lens epithelial cells (LECs, SRA 01/04) were cultured with 30 mM or 5.5 mM glucose, and AMPK activator (AICAR) and inhibitor (Compound C) were applied to further investigate the regulatory role of AMPK on autophagy.Compared with ARC patients, the expression of autophagy-related genesDown-regulation of AMPK-FOXO3 and AMPK-TFEB induced autophagy activity was found in both LECs of anterior capsule from DC patients and SRA 01/04 cells under HG condition, which may be the underlying mechanism of DC formation. Thus, targeting AMPK-induced autophagy may be a potential therapeutic approach for diabetic cataract. |
| Databáze: | OpenAIRE |
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