凝血酶抑制神经细胞突起生长的研究

STUDY ON THE MECHANISMS OF THROMBIN TO INHIBIT NEURITE OUTGROWTH

本实验研究了凝血酶抑制CHP-100原始神经外胚叶瘤细胞神经分化的信号传导机制。凝血酶能抑制CHP-100细胞在无血清培养中神经突起的生长,这种作用与凝血酶激活细胞内磷酸肌醇/钙离子信号传导途径有关。凝血酶明显刺激Ins(1,4,5)P3的产生及细胞内游离钙离子浓度的升高。凝血酶的抑制剂水蛭素能抑制凝血酶引起的钙离子反应,并能拮抗凝血酶抑制CHP-100细胞神经突起生长的作用。结果提示,凝血酶信号传导系统可能在神经系统生长发育中具有重要调节作用。

In the present study, we investigated the effects and signal transduction mecha-nisms of thrombin on neuronal differentiation of human primitive neuroectodermal tu-mor cell lineCHP--100. Thrombin inhibited neurite outgrowth of CHP-100 cells in cul-ture induced by serum removal. The inhibitory effects were found to be associated withactivation of phosphatidylinositol turnover/ calcium mobilization signal transductionpathway by thrombin, since stimulation with thrombin induced significant inositol-1,4, 5 trisphosphate accumulation and intracellular free calcium transient in CHP--100cells. In addition, the most potent inhibitor of thrombin hirudin, which reversed the inhibitory effect of thrombin on neurite outgrowth of CHP-100 cells, also inhibitedthrombin-stimulated calcium transient. These results suggest a specific role of thrombinsignal transduction pathway in the regulation of neuronal differentiation.