Marano C W, Laughlin K V, Russo L M, Mullin J M
Lankenau Medical Research Center, Wynnewood, PA 19096, USA.
Biochem Biophys Res Commun. 1995 Apr 17;209(2):669-76. doi: 10.1006/bbrc.1995.1551.
The transepithelial paracellular permeability of an epithelium formed by LLC-PK1 cells increases upon activation of protein kinase C (PKC) by the phorbol ester tumor promoter, TPA, or in response to the cytokine tumor necrosis factor-alpha (TNF). Until recently, however, we have not been able to inhibit the permeability effects of TPA or TNF using any of the currently available serine-threonine kinase inhibitors. In this study we report the treatment of epithelial cell sheets with the selective PKC inhibitor bisindolylmaleimide, GF109203X, completely prevents the TPA-induced but not the TNF-alpha induced increase in tight junction permeability. While PKC-alpha still translocates from the cytosol to the membrane of TPA-stimulated epithelial cells overall PKC activity in the membrane fraction is markedly reduced in the presence of GFX.
佛波酯肿瘤启动子TPA激活蛋白激酶C（PKC）或细胞因子肿瘤坏死因子-α（TNF）作用后，由LLC-PK1细胞形成的上皮细胞的跨上皮细胞旁通透性会增加。然而，直到最近，我们还无法使用任何现有的丝氨酸-苏氨酸激酶抑制剂来抑制TPA或TNF的通透性效应。在本研究中，我们报告用选择性PKC抑制剂双吲哚马来酰亚胺GF109203X处理上皮细胞片，可完全阻止TPA诱导的紧密连接通透性增加，但不能阻止TNF-α诱导的增加。虽然PKC-α仍从胞质溶胶转位到TPA刺激的上皮细胞膜上，但在存在GFX的情况下，膜组分中的总体PKC活性显著降低。
