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首页> 外文期刊>Cellular Physiology and Biochemistry >Mitogenic signal of epidermal growth factor in chick embryo hepatocytes: Role of PKC alpha
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Mitogenic signal of epidermal growth factor in chick embryo hepatocytes: Role of PKC alpha

机译：表皮生长因子在鸡胚肝细胞中的促有丝分裂信号：PKCα的作用

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摘要

In the present study we investigated the role of two isoforms of protein kinase C in the mitogenic signal of epidermal growth factor (EGF) in primary culture of chick embryo hepatocytes. The down-regulation of PKC alpha by long-term exposure to phorbol myristate acetate (PMA) provoked a reduced mitogenic response to EGF while the down-regulation of PKC epsilon with oligonucleotide antisense had no effect on the stimulation of DNA synthesis, assayed as thymidine incorporation. EGF enhanced H3 diacylglycerol (DAG) production by cells preincubated with H3myristic acid, but did not increase the production of inositol 1-4-5-trisphosphate (IP3). EGF produced an increase in the release of arachidonic acid and prostaglandin E2 (PGE2) in the extracellular medium. The increase was blocked by specific inhibitors (quinacrine and AACOCF3) of phospholipase A2 (PLA2) and was inhibited by down-regulation of PKC alpha, demostrating that this isoform is involved in arachidonic acid production. DAG and arachidonic acid produced an additional effect on thymidine incorporation. The treatment with PLA2 inhibitors, which block the increase in arachidonic acid, decreased the effect of EGF on DNA synthesis. These results suggest that in chick embryo hepatocytes PKC alpha is the main isoform involved in EGF-induced DNA synthesis. Its rapid activation is dependent on DAG production and induces an increased production of arachidonic acid and prostaglandin which are involved in the mitogenic activity. copyright (C) 2000 S. Karger AG. Basel. [References: 37]
机译：在本研究中，我们调查了鸡胚肝细胞原代培养中蛋白激酶C的两个同工型在表皮生长因子（EGF）的有丝分裂信号中的作用。长期暴露于佛波肉豆蔻酸酯乙酸盐（PMA）对PKCα的下调引起对EGF的促有丝分裂反应降低，而寡核苷酸反义对PKC epsilon的下调对DNA合成的刺激没有影响，测定为胸苷成立。 EGF通过与H3肉豆蔻酸预孵育的细胞增强了H3二酰基甘油（DAG）的产生，但并未增加肌醇1-4-5-三磷酸（IP3）的产生。 EGF使细胞外培养基中花生四烯酸和前列腺素E2（PGE2）的释放增加。这种增加被磷脂酶A2（PLA2）的特定抑制剂（奎纳克林和AACOCF3）阻止，并被PKCα的下调抑制，这几乎表明该同工型与花生四烯酸的产生有关。 DAG和花生四烯酸对胸腺嘧啶核苷的掺入产生了额外的影响。用PLA2抑制剂处理可阻止花生四烯酸的增加，从而降低了EGF对DNA合成的影响。这些结果表明在鸡胚肝细胞中，PKCα是参与EGF诱导的DNA合成的主要同工型。它的快速活化取决于DAG的产生，并诱导涉及有丝分裂活性的花生四烯酸和前列腺素的产生增加。版权（C）2000 S. Karger AG。巴塞尔[参考：37]

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