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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
Author(s) -
Li Rongyu,
Reiser Georg
Publication year - 2011
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2011.07317.x
Subject(s) - staurosporine , phosphorylation , microbiology and biotechnology , cytoprotection , ceramide , kinase , protein kinase a , biology , extracellular , p38 mitogen activated protein kinases , mapk/erk pathway , protein kinase c , crystallin , programmed cell death , intracellular , biochemistry , oxidative stress , apoptosis
J. Neurochem. (2011) 118 , 354–364. 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.