Yong V W
Department of Neurology and Neurosurgery, McGill University, Montreal, Quebec, Canada.
J Neurol Sci. 1992 Aug;111(1):92-103. doi: 10.1016/0022-510x(92)90117-4.
While several mitogens for astrocytes have been described, the signal transduction pathway(s) that mediates their proliferative effect remains unclear; in this report, a major role for the protein kinase C (PKC) system is suggested by several lines of evidence. Firstly, biologically active phorbol esters, 4 beta-phorbol-12,13-dibutyrate and phorbol-12-myristate-13-acetate, increase the proliferation of astrocytes as determined by [3H]thymidine incorporation or bromodeoxyuridine immunofluorescence; this effect is not reproduced by a phorbol ester that binds to PKC but does not activate it (4 alpha-phorbol-12,13-didecanoate). Secondly, 2 relatively selective inhibitors of PKC, H7 and staurosporine, attenuate the basal rate of proliferation of astrocytes in concentrations that were not cytotoxic to cells. Thirdly, mitogen-enhanced proliferation of astrocytes can be blocked by PKC inhibitors; this is observed for all astrocyte mitogens tested. Fourthly, measurements of PKC enzyme activity in astrocytes in response to serum-mitogenic factors, or to staurosporine, revealed a statistically significant correlation with proliferation rate. The mediation by PKC is not dependent on species- or age factors, since neonatal mouse or adult human astrocytes gave comparable results. The results have relevance to normal development and reactive gliosis post-injury, 2 conditions where astrocytes undergo proliferation, and to glioma growth.
虽然已经描述了几种星形胶质细胞的促有丝分裂原，但其介导增殖效应的信号转导途径仍不清楚；在本报告中，多条证据表明蛋白激酶C（PKC）系统起主要作用。首先，具有生物活性的佛波酯，4β-佛波醇-12,13-二丁酸酯和佛波醇-12-肉豆蔻酸酯-13-乙酸酯，通过[3H]胸苷掺入或溴脱氧尿苷免疫荧光测定，可增加星形胶质细胞的增殖；一种与PKC结合但不激活它的佛波酯（4α-佛波醇-12,13-癸酸酯）不会产生这种效应。其次，两种相对选择性的PKC抑制剂H7和星形孢菌素，在对细胞无细胞毒性的浓度下，可减弱星形胶质细胞的基础增殖速率。第三，PKC抑制剂可阻断促有丝分裂原增强的星形胶质细胞增殖；在所有测试的星形胶质细胞促有丝分裂原中均观察到这一现象。第四，对星形胶质细胞中PKC酶活性响应血清促有丝分裂因子或星形孢菌素的测量显示，其与增殖速率具有统计学上的显著相关性。PKC的介导作用不依赖于物种或年龄因素，因为新生小鼠或成人星形胶质细胞得到了类似的结果。这些结果与正常发育、损伤后的反应性胶质增生（星形胶质细胞发生增殖的两种情况）以及胶质瘤生长有关。
