ARREST OF EPIDERMAL GROWTH FACTOR-DEPENDENT GROWTH IN FETAL HEPATOCYTES AFTER ETHANOL EXPOSURE
ARREST OF EPIDERMAL GROWTH FACTOR-DEPENDENT GROWTH IN FETAL HEPATOCYTES AFTER ETHANOL EXPOSURE
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DOI：
10.1172/jci114296
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发表时间：
1989-10-01
影响因子：
15.9
通讯作者：
SCHENKER, S
中科院分区：
文献类型：
--
作者：
HENDERSON, GI;BASKIN, GS;SCHENKER, S
胎儿肝细胞在体外暴露于乙醇会阻断表皮生长因子（EGF）依赖性细胞复制。为了确定这种生长停滞的可能机制，我们确定了乙醇对 EGF 结合和 EGF 受体 (EGF-R) 水平的影响。在暴露于乙醇（1.7 mg/ml，31 mM）24小时期间，细胞复制被完全阻断，而每个细胞的EGF结合加倍。这种效应对于 EGF 并不具有特异性，但对于胰岛素、转铁蛋白和胰高血糖素的结合有不同程度的增加。乙醇暴露 6 小时后，EGF 结合显着增加，并且生长停滞和增强的 EGF 结合在乙醇戒断 12 小时内逆转。观察到“高”和“低”亲和力位点均增加，而表观 Kd 没有变化。在暴露于乙醇的细胞中，总RNA、β-肌动蛋白mRNA和EGF-R mRNA增加了50-70%。然而，通过[35S]甲硫氨酸掺入直接测量EFG-R合成率显示对照细胞和乙醇暴露细胞之间没有差异。乙醇暴露显着改变了 EFG-R 的内化。 2小时孵育导致对照细胞中57%的配体内化，而在乙醇暴露的细胞中仅31%的结合EGF内化。因此，增强的 EGF 结合可能是由于内化效率降低所致。
Exposure of the fetal hepatocyte to ethanol in vitro blocks epidermal growth factor (EGF)-dependent cell replication. To define possible mechanisms for this growth arrest, we determined the effects of ethanol on EGF binding and EGF receptor (EGF-R) levels. During a 24-h exposure to ethanol (1.7 mg/ml, 31 mM), cell replication was completely blocked while EGF binding per cell doubled. This effect was not specific for EGF, with variable degrees of increased binding noted for insulin, transferrin, and glucagon. Significantly increased EGF binding was seen after 6 h of ethanol exposure, and both growth arrest and enchanced EGF binding were reversed within 12 h of ethanol withdrawal. Increases in both "high" and "low" affinity sites were seen, with not changes in the apparent Kd''s. Total RNA, .beta.-actin mRNA, and EGF-R mRNA were increased 50-70% in ethanol exposed cells. However, direct measurements of EFG-R synthesis rates by [35S] methionine incorporation revealed no differences between control and ethanol exposed cells. Internalization of EFG-R was significantly altered by ethanol exposure. A 2-h incubation resulted in the internalization of 57% of the ligand in control cells, while only 31% of bound EGF was internalized in the ethanol exposed cells. Thus, the enhanced EGF binding may be due to decreased efficiency of internalization.