Gschwendt M, Fürstenberger G, Rose-John S, Rogers M, Kittstein W, Pettit G R, Herald C L, Marks F
Department of Biochemistry, German Cancer Research Center Heidelberg, FRG.
Carcinogenesis. 1988 Apr;9(4):555-62. doi: 10.1093/carcin/9.4.555.
The macrocyclic lactone bryostatin 1 activates protein kinase C as effectively as the phorbol ester 12-O-tetradecanoyl-phorbol-13-acetate (TPA). Nevertheless, there are only certain TPA-effects that can be induced by bryostatin 1. These include stimulation of epidermal DNA synthesis and alkaline phosphatase activity in vivo as well as activation of the Ca2+-independent, phospholipid-requiring phosphorylation of an epidermal protein in a cell-free system. Various other TPA-effects in vivo and in vitro, which are not mimicked by bryostatin 1 can be inhibited by applying bryostatin 1 30 min prior to TPA. TPA-effects suppressible by bryostatin 1 include the Ca2+-dependent stimulation of arachidonic acid and prostaglandin E2 release, of ornithine decarboxylase (ODC) activity and ODC-mRNA expression and of transglutaminase activity in keratinocytes in vivo and/or in vitro and, in addition, Epstein-Barr virus induction in Raji cells. The same is true for the conversion step (first stage of promotion) of multistage carcinogenesis. In contrast to the TPA induction of arachidonic acid and prostaglandin E2 release and of transglutaminase activity, induction by the Ca2+-ionophore and by high Ca2+-shift, respectively, are not significantly inhibited by bryostatin 1. We suggest that bryostatin 1 might inhibit a specific 'Ca2+-component' of TPA action.
大环内酯类苔藓抑素1激活蛋白激酶C的效果与佛波酯12 - O - 十四烷酰佛波醇 - 13 - 乙酸酯（TPA）一样有效。然而，苔藓抑素1只能诱导某些TPA效应。这些效应包括体内表皮DNA合成的刺激和碱性磷酸酶活性的增强，以及在无细胞体系中表皮蛋白的不依赖钙、需要磷脂的磷酸化的激活。在TPA之前30分钟应用苔藓抑素1，可以抑制体内和体外各种其他未被苔藓抑素1模拟的TPA效应。苔藓抑素1可抑制的TPA效应包括体内和/或体外角质形成细胞中花生四烯酸和前列腺素E2释放、鸟氨酸脱羧酶（ODC）活性和ODC - mRNA表达以及转谷氨酰胺酶活性的钙依赖性刺激，此外还有Raji细胞中爱泼斯坦 - 巴尔病毒的诱导。多阶段致癌作用的转化步骤（促进的第一阶段）也是如此。与TPA诱导花生四烯酸和前列腺素E2释放以及转谷氨酰胺酶活性不同，分别由钙离子载体和高钙转移诱导的作用不受苔藓抑素1的显著抑制。我们认为苔藓抑素1可能抑制TPA作用的一种特定“钙成分”。
