Arrest of epidermal growth factor-dependent growth in fetal hepatocytes after ethanol exposure

G. I. Henderson, G. S. Baskin, J. Horbach, P. Porter, S. Schenker

Research output: Contribution to journalArticlepeer-review

55 Scopus citations

Abstract

Exposure of the fetal rat 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 enhanced EGF binding were reversed within 12 h of ethanol withdrawal. Increases in both 'high' and 'low' affinity sites were seen, with no changes in the apparent K(d)'s. Total RNA, β-actin mRNA, and EGF-R mRNA were increased 50-70% in ethanol exposed cells. However, direct measurements of EGF-R synthesis rates by [35S]methionine incorporation revealed no differences between control and ethanol exposed cells. Internalization of EGF-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.

Original languageEnglish (US)
Pages (from-to)1287-1294
Number of pages8
JournalJournal of Clinical Investigation
Volume84
Issue number4
DOIs
StatePublished - 1989
Externally publishedYes

ASJC Scopus subject areas

  • Medicine(all)

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