Jelkmann W, Huwiler A, Fandrey J, Pfeilschifter J
Department of Physiology, University of Bonn, Germany.
Biochem Biophys Res Commun. 1991 Sep 30;179(3):1441-8. doi: 10.1016/0006-291x(91)91734-t.
The role of protein kinase C (PKC) in the control of erythropoietin (Epo) production was studied using the human hepatoma cell line HepG2. Inhibition of PKC by staurosporine and the selective PKC inhibitor CGP 41251 significantly reduced Epo formation. No inhibition occurred with the inactive staurosporine derivative CGP 42700. Treatment with phorbol 12-myristate 13-acetate (PMA) for 24 h dose-dependently inhibited Epo formation, thus suggesting that down-regulation of PKC might be responsible for this inhibition. Immunoblotting experiments showed that incubation of HepG2 cells with PMA for 24 h resulted in a selective and almost complete down-regulation of PKC-alpha. Thus, PKC-alpha may play a permissive role in Epo synthesis in HepG2 cells.
利用人肝癌细胞系HepG2研究了蛋白激酶C（PKC）在促红细胞生成素（Epo）产生调控中的作用。星形孢菌素和选择性PKC抑制剂CGP 41251对PKC的抑制作用显著降低了Epo的生成。无活性的星形孢菌素衍生物CGP 42700未产生抑制作用。用佛波醇12-肉豆蔻酸酯13-乙酸酯（PMA）处理24小时剂量依赖性地抑制了Epo的生成，因此提示PKC的下调可能是这种抑制作用的原因。免疫印迹实验表明，将HepG2细胞与PMA孵育24小时导致PKC-α选择性且几乎完全下调。因此，PKC-α可能在HepG2细胞的Epo合成中起允许作用。
