Jones K T, Sharpe G R
Department of Dermatology, University of Liverpool, England.
J Cell Physiol. 1994 May;159(2):324-30. doi: 10.1002/jcp.1041590215.
The responsiveness of normal human keratinocytes to different modulators of protein kinase C (PKC) was investigated. The PKC agonist TPA, staurosporine (a non-specific inhibitor), and Ro31-8220 (a specific inhibitor) were studied for effect on cell morphology, growth rate, involucrin expression, and intracellular calcium levels. Surprisingly the response to nanomolar concentrations of staurosporine was similar to TPA and induced a fusiform morphology, inhibited growth, increased involucrin levels, and raised intracellular calcium. Staurosporine also increased the number of cornified envelopes, and its action therefore appeared identical to TPA. In contrast, Ro31-8220 had little effect on morphology or growth and blocked both the TPA-induced growth inhibition and calcium rise. Ro31-8220 had no effect on staurosporine-induced growth inhibition but partially reduced its associated calcium rise. These results suggest PKC activation is required for keratinocyte differentiation and that staurosporine acts like a PKC agonist to give a similar effect as TPA. Specific inhibition of PKC by Ro31-8220 inhibits TPA-induced differentiation.
研究了正常人角质形成细胞对蛋白激酶C（PKC）不同调节剂的反应性。研究了PKC激动剂佛波酯（TPA）、星形孢菌素（一种非特异性抑制剂）和Ro31 - 8220（一种特异性抑制剂）对细胞形态、生长速率、兜甲蛋白表达和细胞内钙水平的影响。令人惊讶的是，对纳摩尔浓度星形孢菌素的反应与TPA相似，可诱导梭形形态、抑制生长、增加兜甲蛋白水平并升高细胞内钙。星形孢菌素还增加了角质包膜的数量，因此其作用似乎与TPA相同。相比之下，Ro31 - 8220对形态或生长几乎没有影响，并阻断了TPA诱导的生长抑制和钙升高。Ro31 - 8220对星形孢菌素诱导的生长抑制没有影响，但部分降低了其相关的钙升高。这些结果表明角质形成细胞分化需要PKC激活，并且星形孢菌素的作用类似于PKC激动剂，产生与TPA相似的效果。Ro31 - 8220对PKC的特异性抑制可抑制TPA诱导的分化。
