Tranque P, Robbins R, Naftolin F, Andrade-Gordon P
Department of Obstetrics and Gynecology, Yale University School of Medicine, New Haven, Connecticut 06510.
Glia. 1992;6(3):163-71. doi: 10.1002/glia.440060303.
Two plasminogen activators (PAs): tissue-type plasminogen activator (t-PA) and urokinase-type plasminogen activator (u-PA), as well as the type-1 plasminogen activator inhibitor (PAI-1) are synthesized and secreted by rat astrocytes. Preliminary studies suggest that PA activity plays a role in astrocyte development and differentiation. We have examined the regulation of the PA system by the cAMP-dependent protein kinase (PKA) and protein kinase C (PKC) in purified rat astrocyte cultures. PKA activity was increased by exposing cultured astrocytes to forskolin or dibutyryl cyclic AMP, whereas PKC activity was stimulated with phorbol-12-myristate 13-acetate (PMA). Activation of both second-messenger pathways produced a time- and dose-dependent increase in the total PA activity. However, based on SDS-PAGE/zymography we found that forskolin increased t-PA activity and reduced u-PA activity, whereas PMA treatment caused a significant increase in u-PA activity without altering t-PA activity. Reverse zymography analysis revealed that astrocyte PAI-1 activity is decreased by forskolin and increased by PMA. Together, these results demonstrate that the components of the PA system in rat astrocytes are independently and reciprocally regulated by PKA and PKC. Our findings raise the possibility that the plasminogen activator system could be involved in some of the actions of growth factors and/or neuromodulators that modulate PKC or PKA in astrocytes.
两种纤溶酶原激活剂（PAs）：组织型纤溶酶原激活剂（t-PA）和尿激酶型纤溶酶原激活剂（u-PA），以及1型纤溶酶原激活剂抑制剂（PAI-1）由大鼠星形胶质细胞合成并分泌。初步研究表明，PA活性在星形胶质细胞的发育和分化中起作用。我们研究了纯化的大鼠星形胶质细胞培养物中，环磷酸腺苷依赖性蛋白激酶（PKA）和蛋白激酶C（PKC）对PA系统的调节作用。通过将培养的星形胶质细胞暴露于福斯高林或二丁酰环磷酸腺苷来增加PKA活性，而用佛波醇-12-肉豆蔻酸酯13-乙酸酯（PMA）刺激PKC活性。两种第二信使途径的激活均使总PA活性产生时间和剂量依赖性增加。然而，基于十二烷基硫酸钠-聚丙烯酰胺凝胶电泳/酶谱分析，我们发现福斯高林增加了t-PA活性并降低了u-PA活性，而PMA处理导致u-PA活性显著增加，而不改变t-PA活性。反向酶谱分析显示，福斯高林降低了星形胶质细胞PAI-1活性，而PMA增加了该活性。总之，这些结果表明，大鼠星形胶质细胞中PA系统的成分受到PKA和PKC的独立且相互调节。我们的研究结果提出了一种可能性，即纤溶酶原激活剂系统可能参与了一些在星形胶质细胞中调节PKC或PKA的生长因子和/或神经调节剂的作用。
