佛波酯通过蛋白激酶C对培养的兔主动脉平滑肌细胞中DNA合成的抑制作用。

Inhibition of DNA synthesis by phorbol esters through protein kinase C in cultured rabbit aortic smooth muscle cells.

作者信息

Kariya K, Fukumoto Y, Tsuda T, Kawahara Y, Fukuzaki H, Yamamoto T, Takai Y

出版信息

FEBS Lett. 1987 Jun 8;217(1):69-73. doi: 10.1016/0014-5793(87)81245-0.

Abstract

In cultured rabbit aortic smooth muscle cells (SMC), 12-O-tetradecanoylphorbol-13-acetate (TPA) induced DNA synthesis in the presence of plasma-derived serum to a small extent, but inhibited markedly the rabbit whole blood serum (WBS)-, platelet-derived growth factor (PDGF)- and epidermal growth factor-induced DNA synthesis. Phorbol-12,13-dibutyrate (PDBu) mimicked this antiproliferative action of TPA, but 4 alpha-phorbol-12,13-didecanoate was inactive in this capacity. Prolonged treatment of the cells with PDBu caused the partial down-regulation of protein kinase C. In these protein kinase C-reduced cells, WBS still induced DNA synthesis, but TPA did not inhibit the WBS-induced DNA synthesis. We have previously shown that protein kinase C is involved at least partially in the PDGF-induced DNA synthesis in rabbit aortic SMC. The present results together with this earlier observation suggest that protein kinase C has not only a proliferative but also an antiproliferative action in rabbit aortic SMC.

摘要

在培养的兔主动脉平滑肌细胞（SMC）中，12 - O - 十四烷酰佛波醇 - 13 - 乙酸酯（TPA）在存在血浆源性血清的情况下能在一定程度上诱导DNA合成，但显著抑制兔全血血清（WBS）、血小板衍生生长因子（PDGF）和表皮生长因子诱导的DNA合成。佛波醇 - 12,13 - 二丁酸酯（PDBu）模拟了TPA的这种抗增殖作用，但4α - 佛波醇 - 12,13 - 二癸酸酯在这方面无活性。用PDBu对细胞进行长时间处理会导致蛋白激酶C部分下调。在这些蛋白激酶C减少的细胞中，WBS仍能诱导DNA合成，但TPA不再抑制WBS诱导的DNA合成。我们之前已表明蛋白激酶C至少部分参与兔主动脉SMC中PDGF诱导的DNA合成。目前的结果与这一早期观察结果共同表明，蛋白激酶C在兔主动脉SMC中不仅具有增殖作用，还具有抗增殖作用。