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Effect of chronic ethanol feeding on intracellular signal transduction process in hepatocytes

慢性乙醇喂养对肝细胞内信号转导过程的影响

基本信息

批准号：
04670441
负责人：
HIGASHI Katsuyoshi
金额：
$ 1.28万
依托单位：
Nagoya City University
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1992
资助国家：
日本
起止时间：
1992 至 1994
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-04670441/
关键词：
chronic ethanol-fed rats hepatocytes signal transduction phospholipase C ethanol vasopressin protein kinase C protein kinase A Phosphdipase C protein kiuaseC protein kiuaseA protein kiuase C protein kimose A vasopvessin 細胞内Ca^<

项目摘要

Effect of chronic ethanol feeding on phospholipase C (PLC) -mediated signal transduction processes in isolated rat hepatocytes. Ethanol-induced phospholipase C activation(intracellular Ca^<2+> ([Ca^<2+>]c) mobilization and inositol-trisphosphate (IP3) accumulation)was unaffected in the cells from control and chronically ethanol-fed rats. However, the responses to ethanol was more sustained in the cells from ethanol-fed rats. In intact cells, IP3 inctrased to the same levels in both preparations, but [Ca^<2+>] c mobilization was more enhanced in the cells from ethanolfed rats. In the permeabilized cells, IP3-induced Ca^<2+> release was more enhanced and sustained in the cells from ethanol-fed rats, indicating that the sensitivity of IP3 to the receptor and the activity of ATP-dependent Ca^<2+> pump decreased in the Ca^<2+> storage sites by chronic ethanol feeding. Vasopressin-induced PLC activation was inhibited by pretreating with phorbol ester, a protein kinase C activating agent, and was enhanced by cAMP-analog, a protein kinase A activating agent, in both preparations. The sensitivity to these agents was decreased in the cells from ethanol-fed rats. In addition the inhibitory effects of ethanol on the vasopressin-induced PLC activation decreased in the ethanol-fed preparations. These data demonstrated that chronic ethanol feeding causes a tolerance to ethanol and protein kinases in hormone-mediated PLC activation. It is suggested that chronic ethanol causes changes in PLC-mediated signal transduction processes and its cross talk, resulting to affect the expression of cell functions.

慢性乙醇喂养对离体大鼠肝细胞中磷脂酶 C (PLC) 介导的信号转导过程的影响。乙醇诱导的磷脂酶C活化(细胞内Ca 2+ ([Ca 2+ ]c)动员和肌醇三磷酸(IP3)积累)在来自对照和长期乙醇喂养的大鼠的细胞中不受影响。然而，在喂食乙醇的大鼠的细胞中，对乙醇的反应更加持续。在完整细胞中，IP3在两种制剂中增加至相同水平，但[Ca 2+ ] c 动员在来自乙醇喂养的大鼠的细胞中增强得更多。在透化细胞中，IP3诱导的Ca^2+释放在乙醇喂养大鼠的细胞中更加增强和持续，表明长期乙醇喂养在Ca^2+储存位点中IP3对受体的敏感性和ATP依赖性Ca^2+泵的活性降低。在两种制剂中，用佛波酯（一种蛋白激酶 C 激活剂）预处理可抑制加压素诱导的 PLC 激活，并可通过 cAMP 类似物（一种蛋白激酶 A 激活剂）进行增强。喂食乙醇的大鼠细胞对这些药物的敏感性降低。此外，在喂食乙醇的制剂中，乙醇对加压素诱导的 PLC 激活的抑制作用降低。这些数据表明，长期摄入乙醇会导致激素介导的 PLC 激活对乙醇和蛋白激酶产生耐受。研究表明，长期摄入乙醇会导致PLC介导的信号转导过程及其串扰发生变化，从而影响细胞功能的表达。