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2000
Volume 25, Issue 10
  • ISSN: 1566-5240
  • E-ISSN: 1875-5666

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 HO-induced apoptosis of LECs and .

Methods

PAK1 expression was assessed in the anterior capsule of the lens from mice and patients with and without ARC using western blotting and immuno-histochemistry. Human lens epithelial B3 (HLE-B3) cells were pre-treated with EGCG+HO or HO 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 western blotting.

Results

PAK1 expression was significantly lower in ARC LECs than in control LECs. In HLE-B3 cells, EGCG+HO treatment upregulated PAK1 mRNA and protein expression when compared with HO alone. PAK1 overexpression alleviated HO-induced apoptosis in LECs, while low expression weakened EGCG’s protective effects. PAK1 overexpression reduced cleaved caspase-3 expression in HO-treated cells, whereas PAK1 silencing increased its expression in EGCG+HO-treated cells. EGCG decreased cleaved caspase-3 expression in HO-treated cells. These results suggest that PAK1 inhibits cleaved caspase-3 expression, thereby enhancing EGCG’s attenuation of HO-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.

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EGCG Mitigates Apoptosis of Lens Epithelial Cells in Age-Related Cataract via the PAK1/Cleaved Caspase-3 Pathway
Current Molecular Medicine 25, 1269 (2025); https://doi.org/10.2174/0115665240334265250213064823
/content/journals/cmm/10.2174/0115665240334265250213064823
/content/journals/cmm/10.2174/0115665240334265250213064823
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  • Article Type:     Research Article
Keyword(s): Age-related cataract; apoptosis; cleaved caspase-3; EGCG; lens epithelial cells; PAK1

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