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Current Molecular Medicine

Editor-in-Chief

ISSN (Print): 1566-5240
ISSN (Online): 1875-5666

αA- and αB-Crystallins Interact with Caspase-3 and Bax to Guard Mouse Lens Development

Author(s): P. Chen, D.W.-C. Li, E. Wawrousek, J.-P. Liu, L. Zhang, S. Sun, J. Liu, H.-G. Chen, Q. Yan, W.-F. Hu, X.-H. Hu, M. Liu, M. Deng, W. Ji, H. Ma, Z. Cao and L. Gong

Volume 12, Issue 2, 2012

Page: [177 - 187] Pages: 11

DOI: 10.2174/156652412798889036

Price: $65

Abstract

The small heat shock protein, α-crystallin, exists in two isoforms, αA and αB, and displays strong ability against stress-induced apoptosis. Regarding their functional mechanisms, we and others have demonstrated that they are able to regulate members in both caspase and Bcl-2 families. In addition, we have also shown that αA and αB may display differential anti-apoptotic mechanisms under certain stress conditions. While αA-crystallin regulates activation of the AKT signaling pathway, αB negatively regulates the MAPK pathway to suppress apoptosis induced by UV and oxidative stress. Although previous studies revealed that αA and αB could regulate members in both caspase and Bcl-2 families, the molecular mechanism, especially the in vivo regulation still waits to be elucidated. In the present communication, we present both in vitro and in vivo evidence to further demonstrate the regulation of caspase-3 and Bax by αA and αB. First, Surface Plasmon Resonance (SPR) and yeast two-hybrid selection analysis demonstrate that αA and αB directly bind to caspase-3 and Bax with differential affinities. Second, immunohistochemistry reveals that αA and αB regulate caspase-3 and Bax at different developmental stages of mouse embryo. Third, coimmunoprecipitation shows that αA and αB form in vivo interacting complexes with caspase-3 and Bax. Together, our results further confirm that αA and αB regulate caspase-3 and Bax in vitro and in vivo to regulate lens differentiation.

Keywords: αA-crystallin, αB-crystallin, apoptosis, Bax, caspase-3, cataract, lens differentition, lens epithelial cells, homeostasis, cataractogenesis, heat shock proteins, apoptosome formation, morphogenesis, Surface Plasmon Resonance Analysis, immunohistochemistry assay


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