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Lili Gong, Jin-Ping Liu, Mi Deng, Weike Ji, Haili Ma, David W. Li; Regulation Of The Akt Signaling Transduction Pathway By αA-crystallin. Invest. Ophthalmol. Vis. Sci. 2011;52(14):3930. doi: https://doi.org/.
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Cataract is a major ocular disease that causes blindness in many developing countries. Cell apoptosis plays a critical role in cataractogenesis. αA-crystallin (αA) is a structural protein in lens, and it also belongs to the small heat shock protein (Hsp) family which exerts anti-apoptotic function. Mice deficient in αA (αA-/-) develop cataracts in which cell apoptosis was significant detected. AKT is an important survival signal molecule in many cell types. The purpose of the presented study is to explore the possible anti-apoptotic mechanism of αA through regulating the AKT signaling pathway.
Surface plasma resonance analysis and co-immunoprecipitation assay were used to investigate the interactions between αA and AKT in vitro. Electronic gel mobility shifting assay, reverse transcription polymerase chain reaction and Western-blot analysis were utilized to study the activation of AKT signaling pathway in the cellular level. Both αA-overexpressing lens epithelial cell (LEC) lines and LECs derived from αA-/- mice were used as cell models to study the AKT signaling pathway. Cell viability, gene expression and kinase activity were compared between αA-overexpressing and vector transfected LECs during H2O2 treatment.
Our result showed that αA specifically bound to AKT in vitro. Significantly reduced activity of AKT and its downstream targets GSK3β and CREB were detected in LECs derived from αA-/- mice. Overexpression of αA in LECs increased cell viability during H2O2 treatment, which depended on constitutive activation of AKT, GSK3β and CREB.
These observations suggest that αA promotes LECs survival by directly activating the AKT signaling pathway.
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