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Y. Mao, H. Xiang, D.W. Li; Alpha-crystallins Interact with Bax and Bcl-xs to Prevent Staurosporine-induced Apoptosis . Invest. Ophthalmol. Vis. Sci. 2003;44(13):1232.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: Alpha-Crystallins, members of the small heat shock protein family, are distinct antiapoptotic regulators. Regarding the antiapoptotic mechanisms, we have previously demonstrated that alphaB-crystallin prevent stress-induced apoptosis through interactions with procaspase-3 and partially processed procapspase-3 to repress caspase-3 activation and also through negative regulation of MAP kinases. Here, we demonstrate that human alphaA- and alphaB-crystallins prevent staurosporine-induced apoptosis through regulation of Bcl-2 family members. Methods: Human alphaA- and alphaB-crystallins, and the related vector-transfected stable expression clones were established with human lens epithelial cells under G418 screening. Expression of human alphaA- and alphaB-crystallins was determined with Western blot and fluorescence microscopy. The interaction between alpha-crystallins and members of the Bcl-2 family were explored with in vitro GST pulldown assays and in vivo co-immunoprecipitation. Results: Both alpha-crystallins from human lenses bind directly to Bax and Bcl-XS. This binding prevents their translocation from cytosol to mitochondria after staurosporine treatment. alpha-crystallins also block staurosporine-stimulated upregulation of Bak, which is largely accumulated in mitochondria. Consequently, alpha-crystallins block the release of cytochrome C, repress activation of caspase-3 and prevent degradation of PARP. Conclusions:Our results demonstrate that alpha-crystallins prevent staurosporine-induced apoptosis through interactions with members of Bcl-2 family, thus providing another novel antiapoptotic mechanism for alpha-crystallins. Supported by EY 11372 and the Hormel Foundation. None.
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