April 2009
Volume 50, Issue 13
Free
ARVO Annual Meeting Abstract  |   April 2009
Alpha-Crystallins Regulate DNA Damage Pathway to Prevent Stress-Induced Apoptosis of Human Lens Epithelial Cells
Author Affiliations & Notes
  • J. Liu
    Bichemistry & Molecular Biology, University of Nebraska Med Center, Omaha, Nebraska
  • L. Gong
    Bichemistry & Molecular Biology, University of Nebraska Med Center, Omaha, Nebraska
  • Z. Cao
    Bichemistry & Molecular Biology, University of Nebraska Med Center, Omaha, Nebraska
  • M. Deng
    Bichemistry & Molecular Biology, University of Nebraska Med Center, Omaha, Nebraska
  • D. Yuan
    Bichemistry & Molecular Biology, University of Nebraska Med Center, Omaha, Nebraska
  • Q. Yan
    Bichemistry & Molecular Biology, University of Nebraska Med Center, Omaha, Nebraska
  • H.-G. Chen
    Bichemistry & Molecular Biology, University of Nebraska Med Center, Omaha, Nebraska
  • D. W. Li
    Bichemistry & Molecular Biology, University of Nebraska Med Center, Omaha, Nebraska
    Ophthalmology & Visual Sciences, University of Nebraska Medical Center, Omaha, Nebraska
  • Footnotes
    Commercial Relationships  J. Liu, None; L. Gong, None; Z. Cao, None; M. Deng, None; D. Yuan, None; Q. Yan, None; H.-G. Chen, None; D.W. Li, None.
  • Footnotes
    Support  1R01EY015765, UNMC start-up funds
Investigative Ophthalmology & Visual Science April 2009, Vol.50, 5180. doi:
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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)

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Abstract

Purpose: : 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.

Methods: : 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.

Results: : 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.

Conclusions: : Alpha-crystallins suppress the DNA damage pathway to prevent UVA-induced apoptosis.

Keywords: crystallins • cell survival • cataract 
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