March 2012
Volume 53, Issue 14
ARVO Annual Meeting Abstract  |   March 2012
αA-Crystallin Regulates p53-Mediated Signaling Pathway to Prevent Apoptosis of Lens Epithelial Cells and Cataractogenesis
Author Affiliations & Notes
  • Weike Ji
    Biochemistry and Molecular Biology, University of Nebraska Medical Center, OMAHA, Nebraska
  • Footnotes
    Commercial Relationships  Weike Ji, None
  • Footnotes
    Support  NEI Grant 1R01EY018380, Chinese Scholarship Council
Investigative Ophthalmology & Visual Science March 2012, Vol.53, 1043. doi:
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      Weike Ji; αA-Crystallin Regulates p53-Mediated Signaling Pathway to Prevent Apoptosis of Lens Epithelial Cells and Cataractogenesis. Invest. Ophthalmol. Vis. Sci. 2012;53(14):1043.

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      © ARVO (1962-2015); The Authors (2016-present)

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Purpose: : Cataract is a major ocular disease that causes blindness in many developing countries. Studies from our laboratory and many others have shown that apoptosis plays a critical role in cataractogenesis. αA-crystallin (αA), a lens structure protein belongs to the small heat shock protein family that exerts anti-apoptotic functions. Mice deficient in αA (αA-/-) develops cataracts, and cell apoptosis was significant detected in αA-/- lens epithelium even before formation of obvious cataracts. However, the underlying molecular mechanism is largely unknown. The p53 protein plays a pivotal role in activating and integrating apoptosis pathways. The protein level of p53 is tight regulated by Ubiquitination. The purpose of the presented study is to explore the possible anti- apoptotic mechanism of αA through regulating the p53-mediated apoptotic signaling pathway.

Methods: : Co-immunoprecipitation assays were used to investigate interactions between αA and p53. Reverse transcription polymerase chain reaction and Western-blot analysis were utilized to study the regulation of p53 signaling pathway in human lens epithelial cells (HLECs). MTT assay was used to evaluate cell viability under stressed conditions.

Results: : Our results showed that αA could directly bind to p53. Such interaction leads to significantly reduction of p53 level and activity. As a result, expression of its downstream target genes such as Bax was also downregulated. Mechanistically, αA enhances the interaction between p53 and its ubiquitin E3 ligase to promote p53 degradation.

Conclusions: : These observations suggest that one of the mechanisms for αA to protect LECs from apoptosis, thus the lens pathology occurs through negative regulation of p53 functions.

Keywords: apoptosis/cell death • cataract • crystallins 

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