Yue Zhang, Dongmei Su, Zhaoyi Sun, Yanjiang Fu, Xiaoya Chen, Yuzhu Hu, Xiao Zhang, Shunfei Zheng, Xu Ma, Shanshan Hu
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引用次数: 0
Abstract
Background: Oxidative damage and apoptosis of lens epithelial cells (LECs) are the primary factors contributing to the development of age-related cataracts (ARC). The potential protective effects of epigallocatechin gallate (EGCG) on LECs remain unclear despite its remarkable antioxidant and anti-apoptotic properties. The aim of this study was to explore the role of serine/threonine-protein kinase (PAK1) in EGCG-mediated attenuation of H2O2-induced apoptosis of LECs in vivo and in vitro.
Methods: PAK1 expression was assessed in the anterior capsule of the lens from mice and patients with and without ARC using western blotting and immunohistochemistry. Human lens epithelial B3 (HLE-B3) cells were pre-treated with EGCG+H2O2 or H2O2 only, and PAK1 expression was determined using qRT-PCR and western blotting. Apoptosis (following PAK1 overexpression or silencing) and cell survival were assessed using Hoechst 33342 staining and a cell counting Kit-8 assay, respectively. Cleaved caspase-3 was measured in transected cells, aged/young mice, and mice treated with EGCG via western blotting.
Results: PAK1 expression was significantly lower in ARC LECs than in control LECs. In HLE-B3 cells, EGCG+H2O2 treatment upregulated PAK1 mRNA and protein expression when compared with H2O2 alone. PAK1 overexpression alleviated H2O2- induced apoptosis in LECs, while low expression weakened EGCG's protective effects. PAK1 overexpression reduced cleaved caspase-3 expression in H2O2-treated cells, whereas PAK1 silencing increased its expression in EGCG+H2O2-treated cells. EGCG decreased cleaved caspase-3 expression in H2O2-treated cells. These results suggest that PAK1 inhibits cleaved caspase-3 expression, thereby enhancing EGCG's attenuation of H2O2-induced LEC apoptosis.
Conclusion: The PAK1/cleaved caspase-3 pathway plays a key role in EGCG's protective effects on the development of ARC. This provides a new therapeutic target for the use of EGCG in preventing and treating ARC.
期刊介绍：
Current Molecular Medicine is an interdisciplinary journal focused on providing the readership with current and comprehensive reviews/ mini-reviews, original research articles, short communications/letters and drug clinical trial studies on fundamental molecular mechanisms of disease pathogenesis, the development of molecular-diagnosis and/or novel approaches to rational treatment. The reviews should be of significant interest to basic researchers and clinical investigators in molecular medicine. Periodically the journal invites guest editors to devote an issue on a basic research area that shows promise to advance our understanding of the molecular mechanism(s) of a disease or has potential for clinical applications.
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