Institut für Neurobiochemie, Otto-von-Guericke-Universität Magdeburg, Medizinische Fakultät, Leipziger Straße 44, 39120 Magdeburg, Germany.
Neurochem Int. 2012 May;60(6):652-8. doi: 10.1016/j.neuint.2012.02.031. Epub 2012 Mar 5.
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.
我们之前曾报道αA-晶体蛋白和蛋白酶激活受体参与保护星形胶质细胞免受 C2-神经酰胺和星形孢菌素诱导的细胞死亡（Li 等人，2009）。在这里，我们研究了αA-晶体蛋白介导的细胞保护的分子机制。我们发现，模拟αA-晶体蛋白特定磷酸化的突变体的表达增加了星形胶质细胞的保护。然而，模拟αA-晶体蛋白非磷酸化的突变体的表达导致保护丧失。这些数据表明αA-晶体蛋白在 Ser122 和 Ser148 处的磷酸化是保护所必需的。此外，我们探讨了αA-晶体蛋白对星形胶质细胞的细胞保护机制。特异性 p38 和 ERK 抑制剂的应用消除了αA-晶体蛋白过表达对星形胶质细胞的保护作用。因此，p38 和 ERK 通过αA-晶体蛋白参与保护过程。这与我们之前的结果一致，表明 p38 和 ERK 调节蛋白酶激活受体 2（PAR-2）/αB-晶体蛋白介导的细胞保护。此外，我们发现 PAR-2 激活增加了αA-晶体蛋白的表达。因此，内源性αA-晶体蛋白通过调节αA-晶体蛋白的表达和/或磷酸化状态来保护星形胶质细胞。
