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J. Liu, L. Gong, Z. Cao, M. Deng, D. Yuan, Q. Yan, H.-G. Chen, D. W. Li; Alpha-Crystallins Regulate DNA Damage Pathway to Prevent Stress-Induced Apoptosis of Human Lens Epithelial Cells. Invest. Ophthalmol. Vis. Sci. 2009;50(13):5180.
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© ARVO (1962-2015); The Authors (2016-present)
In our previous studies, we have demonstrated that alpha-crystallins can negatively regulate stress-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 regulate the ATR-p53 pathway to prevent UVA-induced apoptosis.
UVA was used to irradiate human lens epithelial cells stably expressing vector, alphaA, and alphaB. Western blot analysis was used for detection of ATR, CHK1/2 and p53 activation. Reporter gene activity assay was used to explore the transactivity of p53. Hoechst staining was used for apoptosis assay.
Human lens epithelial cells expressing either alphaA- or alphaB-crystallin are substantially resistant to UVA-induced apoptosis. UVA-induces activation of ATR and CHK1/2 kinases to activate p53 in vector-transfected cells. However, in alphaA- or alphaB-crystallin-transfected cells, activation of ATR, CHK1/2 kinases and p53 was distinctly suppressed.
Alpha-crystallins suppress the DNA damage pathway to prevent UVA-induced apoptosis.
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