title: Phosphorylation of Ser45 and Ser59 of αB-crystallin and p38/extracellular regulated kinase activity determine αB-crystallin-mediated protection of rat brain astrocytes from C2-ceramide- and staurosporine-induced cell death.
abstract: We previously demonstrated that αB-crystallin and protease-activated receptor (PAR) are involved in protection of astrocytes against C2-ceramide- and staurosporine-induced cell death [Li et al. (2009) J. Neurochem.110, 1433-1444]. Here, we further investigated the mechanism of cytoprotection by αB-crystallin. Our current data revealed that after down-regulation of αB-crystallin by siRNA, cell death caused by C2-ceramide and staurosporine is increased. Furthermore, we investigated the mechanism of cytoprotection of astrocytes by intracellular αB-crystallin. Application of specific inhibitors of p38 and extracellular regulated kinase (ERK) abrogates the protection of astrocytes by over-expression of αB-crystallin. Thus, p38 and ERK contribute to protective processes by αB-crystallin. To reveal the molecular mechanism of αB-crystallin-mediated cytoprotection, we mimicked phosphorylation or unphosphorylation of αB-crystallin. In these experiments, we found that the phosphorylation of αB-crystallin at Ser45 and Ser59 is required for protection. Ser19 phosphorylation of αB-crystallin does not contribute to protection. Moreover, we detected that PAR-2 activation increases the phosphorylation level of αB-crystallin at Ser59, but does not affect the expression level of αB-crystallin. Thus, endogenous αB-crystallin has protective capacity employing a mechanism, which involves regulation of the phosphorylation status of αB-crystallin and p38 and ERK activity. Moreover, we report that PAR-2 activation evokes the phosphorylation of αB-crystallin to increase astrocytes survival.
authors: Institut für Neurobiochemie, Otto-von-Guericke-Universität Magdeburg, Medizinische Fakultät, Magdeburg, Germany.
authors: Rongyu
authors: R
authors: Li
authors: Georg
authors: G
authors: Reiser