title: Specific phosphorylation of αA-crystallin is required for the αA-crystallin-induced protection of astrocytes against staurosporine and C2-ceramide toxicity.
abstract: We previously reported that αA-crystallin and protease-activated receptor are involved in protection of astrocytes against C2-ceramide- and staurosporine-induced cell death (Li et al., 2009). Here, we investigated the molecular mechanism of αA-crystallin-mediated cytoprotection. We found that the expression of mutants mimicking specific phosphorylation of αA-crystallin increases the protection of astrocytes. However, the expression of mutants mimicking unphosphorylation of αA-crystallin results in loss of protection. These data revealed that the phosphorylation of αA-crystallin at Ser122 and Ser148 is required for protection. Furthermore, we explored the mechanism of cytoprotection of astrocytes by αA-crystallin. Application of specific inhibitors of p38 and ERK abrogates the protection of astrocytes by over-expression of αA-crystallin. Thus, p38 and ERK contribute to protective processes by αA-crystallin. This is comparable to our previous results which demonstrated that p38 and ERK regulated protease-activated receptor-2 (PAR-2)/αB-crystallin-mediated cytoprotection. Furthermore, we found that PAR-2 activation increases the expression of αA-crystallin. Thus, endogenous αA-crystallin protects astrocytes via mechanisms, which regulate the expression and/or phosphorylation status of αA-crystallin.
authors.affiliation: Institut für Neurobiochemie, Otto-von-Guericke-Universität Magdeburg, Medizinische Fakultät, Leipziger Straße 44, 39120 Magdeburg, Germany.
authors.forename: Rongyu
authors.initials: R
authors.lastname: Li
authors.forename: Zhihui
authors.initials: Z
authors.lastname: Zhu
authors.forename: Georg
authors.initials: G
authors.lastname: Reiser
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D002470:Cell Survival / Q000187:drug effects; D010766:Phosphorylation / Q000187:drug effects / Q000502:physiology; D061251:Primary Cell Culture; D051381:Rats; D017208:Rats, Wistar; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000633:toxicity; D019311:Staurosporine / Q000633:toxicity*; D038202:alpha-Crystallin A Chain / Q000378:metabolism* / Q000502:physiology
chemical_list: C064769:N-acetylsphingosine; D038202:alpha-Crystallin A Chain; D019311:Staurosporine; D013110:Sphingosine