p38β MAPK affords cytoprotection against oxidative stress-induced astrocyte apoptosis via induction of αB-crystallin and its anti-apoptotic function

The activation of p38 mitogen-activated protein kinases (MAPKs) has been implicated in many cellular processes, such as, inflammation, cell death, and survival. In mammals, four distinct genes encode the four known members of p38 MAPKs, p38 alpha, p38 beta, p38 gamma, and p38 delta. Despite the fact that p38 alpha and p38 beta MAPKs share over 75% homology sequences, they have distinct, perhaps even opposite roles under stress conditions. In our previous report, we showed that p38 beta MAPK is induced in activated astrocytes in the penumbra of the postischemic brain, wherein it was co-localized with alpha B-crystallin and MAPKAPK-2. To investigate the functional significance of p38 beta MAPK in astrocytes, a C6 astroglioma cell line stably over-expressing p38 beta MAPK was generated. In these cells, hydrogen peroxide-induced apoptosis was reduced to 44.3% of that obtained from normal C6 cells. Interestingly, we found that expression of a small heat shock protein, alpha B-crystallin, was significantly increased in these cells, but that the expressions of HSP27 and HSP70 were not. Repression of alpha B-crystallin expression by alpha B-crystallin siRNA transfection suppressed the protective effect and recovered caspase 3 activity, indicating that alpha B-crystallin induction plays a crucial role in the protection against H(2)O(2)-induced apoptosis observed in p38 beta-overexpressing C6 astroglioma cells. We found that the binding between alpha B-crystallin and partially processed caspase-3 (a p24 intermediate) was significantly increased in p38 beta-overexpressing cells, which might result in suppression of caspase 3 activity in these cells. These results indicate that p38 beta confers protection against H(2)O(2)-induced astrocytes apoptosis by inducing a small heat shock protein, alpha B-crystallin, which inhibits caspase-3 activation. (C) 2011 Elsevier Ireland Ltd. All rights reserved.