Rapid effects of phorbol esters on isolated rat adipocytes. Relationship to the action of protein kinase C.
Rapid effects of phorbol esters on isolated rat adipocytes. Relationship to the action of protein kinase C.
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DOI：
10.1111/j.1432-1033.1985.tb08854.x
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发表时间：
1985-05
期刊：
影响因子：
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通讯作者：
G. Skoglund;A. Hansson;M. Ingelman-Sundberg
中科院分区：
文献类型：
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作者：
G. Skoglund;A. Hansson;M. Ingelman-Sundberg
用促进肿瘤的佛波酯处理分离的大鼠脂肪细胞，导致葡萄糖氧化刺激五倍，确定为[1-14C]葡萄糖产生14CO2，并且[14C]葡萄糖合成脂质的速率增加五倍。用 12-O-十四烷酰佛波醇 13-乙酸酯处理细胞增加了细胞摄取 86Rb+ 的速率。磷脂酶 C 还能够刺激葡萄糖氧化速率；磷脂酶 C 和 12-O-十四烷酰佛波醇 13-乙酸酯以非协同方式刺激葡萄糖氧化，表明它们的作用机制相同。活性佛波酯以及部分磷脂酶 C 导致蛋白激酶 C 活性从脂肪细胞的可溶部分转移到颗粒部分。该过程很快，在添加佛波酯后 30 秒内完成，并导致激酶主要出现在线粒体和质膜部分中。脂肪细胞蛋白激酶C的结合特性与佛波酯对脂肪细胞的代谢作用的比较表明，剂量-反应关系与佛波酯的结合不相关，而是观察到蛋白激酶C易位所需的佛波酯的剂量与细胞内效应之间存在相关性。结果表明，蛋白激酶 C 的细胞内易位可能是佛波酯对脂肪细胞作用的触发因素，而酯与蛋白激酶 C 的结合不足以引起这种作用。此外，有人认为蛋白激酶 C 的激活可能部分是激素（例如胰岛素）对脂肪细胞的作用所致。
Treatment of isolated rat adipocytes with tumor-promoting phorbol esters, caused a fivefold stimulation of glucose oxidation, determined as 14CO2 production from [1-14C]glucose and a fivefold increase in the rate of lipid synthesis from [14C]glucose. Treatment of the cells with 12-O-tetradecanoylphorbol 13-acetate increased the rate of 86Rb+ uptake into the cells. Also phospholipase C was able to stimulate the rate of glucose oxidation; phospholipase C and 12-O-tetradecanoylphorbol 13-acetate stimulated glucose oxidation in a non-synergistic fashion, indicating a common mechanism for their action. Active phorbol esters and, in part, also phospholipase C, caused a translocation of protein kinase C activity from the soluble to the particulate fraction of the adipocytes. This process was rapid, being complete 30 s after the addition of phorbol ester, and resulted in the appearance of the kinase mainly in the mitochondrial and plasma membrane fractions. A comparison between the binding characteristics of adipocyte protein kinase C and the metabolic effects of the phorbol esters on the adipocytes revealed that the dose-response relationship did not correlate with binding of the phorbol esters, but, rather, a correlation was observed between the dose of phorbol esters required for translocation of protein kinase C and the intracellular effects. The results indicate that the intracellular translocation of protein kinase C might be a trigger for the effects of phorbol esters on the adipocyte and that binding of the esters to protein kinase C is not a sufficient event to cause this effect. Furthermore, it is suggested that activation of protein kinase C might be partly the action of hormones, such as insulin, on the fat cells.