Lysophosphatidic acid promotes survival and differentiation of rat Schwann cells
Lysophosphatidic acid promotes survival and differentiation of rat Schwann cells
复制标题
DOI：
10.1074/jbc.m213244200
复制
发表时间：
2003-03-14
影响因子：
4.8
通讯作者：
Tennekoon, GI
中科院分区：
文献类型：
--
作者：
Li, YW;Gonzalez, MI;Tennekoon, GI
溶血磷脂酸(LPA)是血清中丰富的成分，通过G蛋白偶联的蛇纹石受体介导多种生物学反应。雪旺细胞表达LPA受体(EDG受体)，一旦激活，有可能通过G(Alphai)激活p21(Ras)和磷脂酰肌醇3-激酶，通过G(Alphaq)激活磷脂酶C，或通过G(q12/13)激活Rho通路。我们发现，血清或LPA加入到血清饥饿的雪旺细胞中，迅速(10分钟)通过Rho介导的途径诱导肌动蛋白应激纤维的出现。此外，LPA还能以G(Alphai)/磷脂酰肌醇3-激酶/MEK/MAPK依赖的方式使雪旺细胞免于凋亡。此外，LPA以G(Alphai)非依赖性的方式促进雪旺细胞髓鞘蛋白P-0的表达，但依赖于蛋白激酶C。通过药理学和过表达的方法，我们发现髓鞘蛋白P-0的表达需要新的同工酶蛋白激酶CDelta。因此，LPA在雪旺细胞中的多重作用(肌动蛋白重组、存活。和髓鞘基因表达)似乎是通过LPA受体激活的不同G蛋白依赖途径来调节的。
Lysophosphatidic acid (LPA; 1-acyl-sn-glycerol-3-phosphate), an abundant constituent of serum, mediates multiple biological responses via G protein-coupled serpentine receptors. Schwann cells express the LPA receptors (Edg receptors), which, once activated, have the potential to signal through G(alphai) to activate p21(ras) and phosphatidylinositol 3-kinase, through G(alphaq) to activate phospholipase C, or through G(q12/13) to activate the Rho pathway. We found that the addition of serum or LPA to serum-starved Schwann cells rapidly (10 min) induced the appearance of actin stress fibers via a Rho-mediated pathway. Furthermore, LPA was able to rescue Schwann cells from apoptosis in a G(alphai)/phosphatidylinositol 3-kinase/MEK/MAPK-dependent manner. In addition, LPA increased the expression of myelin protein P-0 in Schwann cells in a G(alphai)-independent manner but dependent on protein kinase C. By means of pharmacological and overexpression approaches, we found that the novel isozyme protein kinase Cdelta was required for myelin P-0 expression. Thus, the multiple effects of LPA in Schwann cells (actin reorganization, survival. and myelin gene expression) appear to be mediated through the different G protein-dependent pathways activated by the LPA receptor.