Involvement of protein kinase C in the regulation of ornithine decarboxylase mRNA by phorbol esters in rat hepatoma cells.
Involvement of protein kinase C in the regulation of ornithine decarboxylase mRNA by phorbol esters in rat hepatoma cells.
复制标题
DOI：
10.1016/0014-4827(91)90129-i
复制
发表时间：
1991-05
影响因子：
3.7
通讯作者：
A. P. Butler;P. Mar;F. McDonald;R. Ramsay
中科院分区：
文献类型：
--
作者：
A. P. Butler;P. Mar;F. McDonald;R. Ramsay
肿瘤促进剂12-O-十四酰基佛波醇-13-乙酸酯（TPA）刺激靶细胞中鸟氨酸脱羧酶（EC 4.1.1.17; ODC）活性的快速增加。在这里，我们证明，这一过程涉及ODC mRNA的快速积累，这是最大的处理后3小时（3 - 8倍大于对照细胞），并在18小时内衰减到对照水平。TPA对ODC mRNA的刺激作用可被二丁酸佛波酯下调蛋白激酶C（PKC）所阻断。ODC mRNA也被PKC激活剂磷脂酶C和1-油酰基-2-乙酰基-rac-甘油诱导，并被激酶抑制剂（三氟拉嗪、H7和棕榈酰-l-肉毒碱）阻断，这与诱导机制中PKC激活的要求一致。然而，非PKC特异性蛋白激酶抑制剂HA 1004也抑制响应TPA的ODC mRNA的表达，在它不抑制PKC的条件下，表明其他激酶可能参与细胞内信号传导过程。TPA（5.7 ± 0.8 h）或放线菌酮（6.0 h）均未显著改变ODC mRNA的稳定性（对照值= 6.2 ± 1.6 h）。这些结果与用佛波酯肿瘤促进剂处理后改变的mRNA半衰期对ODC mRNA积累的任何贡献不一致。
The tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) stimulates a rapid increase in ornithine decarboxylase (EC 4.1.1.17; ODC) activity in target cells. Here we demonstrate that this process involves a rapid accumulation of ODC mRNA, which is maximal 3 h after treatment (three- to eightfold greater than control cells) and decays to control levels within 18 h. Stimulation of ODC mRNA by TPA is blocked by phorbol dibutyrate down-regulation of protein kinase C (PKC). ODC mRNA was also induced by the PKC activators, phospholipase C and 1-oleoyl-2-acetyl-rac-glycerol, and blocked by kinase inhibitors (trifluoroperazine, H7, and palmitoyl-l-carnitine), consistent with a requirement for PKC activation in the induction mechanism. However, the non-PKC-speciflc protein kinase inhibitor HA1004 also suppressed expression of ODC mRNA in response to TPA, under conditions where it did not inhibit PKC, suggesting that additional kinases may be involved in the intracellular signalling process. The stability of the ODC mRNA (control value = 6.2 ± 1.6 h) is not significantly changed by either TPA (5.7 ± 0.8 h) or by cycloheximide (6.0 h). These results are inconsistent with any contribution from altered mRNA half-life towards the accumulation of ODC mRNA following treatment with phorbol ester tumor promoters.