Gschwendt M, Kittstein W, Marks F
German Cancer Research Center, Institute of Biochemistry, Heidelberg, F.R.G.
Biochem Biophys Res Commun. 1988 Jan 29;150(2):545-51. doi: 10.1016/0006-291x(88)90428-7.
Various biological effects induced by the tumor promoting phorbol ester TPA in mouse skin are comparably suppressed by the immunologically inactive cyclosporine H (CsH) and by the strongly immunosuppressive cyclosporine A (CsA). These effects inhibited include the development of edema, stimulation of alkaline phosphatase activity, DNA and protein synthesis, as well as tumor promotion. Furthermore, CsH, like CsA, inhibits the Ca2+/calmodulin-dependent phosphorylation of the elongation factor 2 (EF-2) in vitro and the TPA-induced increases in the amount of EF-2 in vivo. Similar observations were made using the weak immunosuppressant CsD. We conclude from these results that the ability of cyclosporines to act as immunosuppressants and their ability to inhibit TPA-effects are based on two different mechanisms of action. Inhibition of TPA-effects may involve suppression of calmodulin-dependent processes, such as augmentation and phosphorylation of EF-2.
肿瘤促进剂佛波酯TPA在小鼠皮肤中诱导的各种生物学效应，可被免疫惰性的环孢素H（CsH）和强免疫抑制性的环孢素A（CsA）同等程度地抑制。这些被抑制的效应包括水肿的形成、碱性磷酸酶活性的刺激、DNA和蛋白质合成，以及肿瘤促进作用。此外，CsH与CsA一样，在体外可抑制延伸因子2（EF-2）的Ca2+/钙调蛋白依赖性磷酸化，在体内可抑制TPA诱导的EF-2量的增加。使用弱免疫抑制剂CsD也得到了类似的观察结果。我们从这些结果得出结论，环孢素作为免疫抑制剂的能力及其抑制TPA效应的能力基于两种不同的作用机制。抑制TPA效应可能涉及抑制钙调蛋白依赖性过程，如EF-2的增加和磷酸化。
