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Epidermal growth factor binding in the presence of ethanol
M J Gerhart1, B Y Reed, R L Veech
1Division of Intramural Clinical and Biological Research, National Institute on Alcohol Abuse and Alcoholism, Rockville, MD 20852.
Abstract:
Epidermal growth factor (EGF) is a mitogen which has been shown to stimulate maxillo-facial growth and DNA synthesis. Ethanol has been reported to inhibit cell regeneration in vivo and in vitro and to produce diminished maxillo-facial development in fetal alcohol syndrome. Recent findings from this laboratory have elucidated rapid metabolic changes in the hepatic content of some of the glycolytic intermediates resulting from injection of EGF, ethanol or EGF combined with ethanol in vivo. An immediate effect of EGF in vivo is to increase hepatic tissue content of 3-phosphoglycerate and phosphoenolpyruvate 1.2-1.3 fold when compared to saline treatment. Ethanol however causes a marked fall in the hepatic content of 3-phosphoglycerate and phosphoenolpyruvate 3.2-3.7 fold below saline treated levels. Ethanol in combination with EGF decreases hepatic values for 3-phosphoglycerate and phosphoenolpyruvate 2.0-2.3 fold from saline treated, but elevates the content of phosphoenolpyruvate 1.6 fold over ethanol treatment alone. Such metabolite changes occurring with ethanol treatment have been attributed alternately to redox shifts or to membrane perturbations. We wished to determine whether dimunition of 3-phosphoglycerate and or phosphoenolpyruvate below certain levels perhaps critically necessary for normal mitogenic action of EGF was due in this case to ethanol effects of binding of EGF to the cell membrane.