Alpha-Crystallins Regulate UVA-Induced Apoptosis in the Ocular Lens Through Multiple Signaling Pathways

Abstract

Purpose: : UV is a well known risk factor causing cataractogenesis. UVA-induced apoptosis of lens epithelial cells has been shown an early event of cataractogenesis. The ocular lens normally guards apoptosis of the lens epithelial cells through the function of the lens structure proteins, alpha-crystallins. In our previous studies, we have demonstrated that alpha-crystallins can negatively regulate UVA-induced apoptosis through suppression of the ERK-mediated pathway and activation of the AKT signaling pathway. In the present study, we present evidence to show that alpha-crystallins can inhibit the ATR-p53 pathway to prevent UVA-induced apoptosis.

Methods: : UVA was used to irradiate human lens epithelial cells stably expressing GFP vector, alphaA-GFP, and alphaB-GFP fusion proteins. Western blot analysis was used for detection of ATR and p53 activation. Reporter gene activity assay was used to explore the transactivity of p53. Hoechst staining was used for apoptosis assay.

Results: : Human lens epithelial cells expressing either alphaA- or alphaB-crystallin are substantially resistant to UVA-induced apoptosis. UVA-induces activation of ATR and p38 kinases to activate p53 in vector-transfected cells. However, in alphaA- or alphaB-crystallin-transfected cells, activation of ATR, p38 MAPK and p53 was distinctly suppressed.

Conclusions: : Alpha-crystallins suppress the p38 kinase and ATR-p53 pathways to prevent UVA-induced apoptosis.

Keywords: apoptosis/cell death • oxidation/oxidative or free radical damage • crystallins