Stanimirovic D B, Ball R, Durkin J P
Institute for Biological Sciences, National Research Council of Canada, Ottawa, ONT, Canada.
Neurosci Lett. 1995 Sep 15;197(3):219-22. doi: 10.1016/0304-3940(95)11941-o.
The proliferation of cerebral endothelial cells is a crucial step in neural angiogenesis and is a process responsive to changes in the surrounding environment. Serum-free medium conditioned by rat cortical astrocytes was found to accelerate DNA synthesis, induce transient activation of protein kinase C (PKC), and increase the endogenous phosphorylation of the PKC-specific substrate, the 85 kDa MARCKS protein, in rat cerebromicrovascular endothelial cells (RCEC). The stimulatory factor(s) in astrocyte conditioned media (ACM) were heat- and trypsin-sensitive and found to have an apparent molecular weight greater than 10 kDa. The potent PKC activator, 12-O-tetradecanoyl phorbol 13-acetate (TPA), also stimulated RCEC proliferation, whereas the inhibition of PKC by staurosporine caused a concomitant loss in ACM-induced PKC translocation, MARCKS protein phosphorylation and DNA synthesis. These findings implicate PKC activation as a critical early event in cerebral endothelial cell proliferation triggered by astrocyte-derived mitogen(s).
脑内皮细胞的增殖是神经血管生成中的关键步骤，且是一个对周围环境变化有反应的过程。研究发现，经大鼠皮质星形胶质细胞条件培养的无血清培养基可加速DNA合成，诱导蛋白激酶C（PKC）短暂激活，并增加大鼠脑血管内皮细胞（RCEC）中PKC特异性底物85 kDa的富含丙氨酸的蛋白激酶C底物蛋白（MARCKS蛋白）的内源性磷酸化。星形胶质细胞条件培养基（ACM）中的刺激因子对热和胰蛋白酶敏感，且其表观分子量大于10 kDa。强效PKC激活剂12-O-十四酰佛波醇-13-乙酸酯（TPA）也可刺激RCEC增殖，而星形孢菌素对PKC的抑制会导致ACM诱导的PKC易位、MARCKS蛋白磷酸化和DNA合成同时丧失。这些发现表明PKC激活是星形胶质细胞衍生的有丝分裂原触发的脑内皮细胞增殖中的关键早期事件。
