αB-crystallin suppresses oxidative stress-induced astrocyte apoptosis by inhibiting caspase-3 activation

alpha B-crystallin is a member of the small heat shock proteins, which is abundantly expressed in various vertebrate tissues including the central nervous system. In our previous report, we showed alpha B-crystallin induction in activated astrocytes in the postischemic brain and in H2O2-treated primary astrocyte cultures. To investigate the functional significance of alpha B-crystallin induction in astrocytes, we generated a stable C6 astroglioma cell line overexpressing alpha B-crystallin. In these cells, hydrogen peroxide-induced apoptosis was reduced by 60% compared to parent cells. Furthermore, the repression of aB-crystallin expression by alpha B-crystallin siRNA transfection suppressed this protective effect, indicating that alpha B-crystallin is responsible for the protection against H2O2-induced apoptosis in C6 astroglioma cells. Similar level of aggravation in H2O2-induced apoptosis was observed in primary astrocyte cultures when alpha B-crystallin expression was suppressed by alpha B-crystallin siRNA transfection, confirming the importance of alpha B-crystallin. In addition, the induction of caspase-3 activity after H2O2 treatment was markedly suppressed in alpha B-crystallin-overexpressing cells, and immunoprecipitation proved binding between alpha B-crystallin and partially processed caspase-3 (a p24 intermediate). These results indicate that alpha B-crystallin confers protection against hydrogen peroxide-induced astrocytes apoptosis in part by inhibiting caspase-3 activation. (C) 2009 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.