Inhibition of hepatocyte proliferation in vivo by a glycopeptide from rat serum.
The activity of a glycopeptide prepared from rat serum by treatment with trypsin and ultrafiltration was investigated in several in vivo proliferation systems. In baby rat hepatocytes synchronized by a subcutaneous injection of casein solution it caused a G1-S block, stopping cells at the end of the G1 phase and sending them back to the G0 phase. The glycopeptide also caused a G1-S block in young adult rats during the first semi-synchronized wave of proliferation that followed partial hepatectomy. Inhibition of hepatocyte proliferation by the glycopeptide was suppressed by blood proteins from normal rats but not from acute phase rats. Alpha 1-acid glycoprotein, an acute phase protein, increased this inhibition and reversed the antagonistic effect of normal blood proteins. In normal baby rats a G1-S block of non-synchronously proliferating hepatocytes was produced in two situations in which the antagonistic effect of normal blood proteins was eliminated: after treatment of the glycopeptide with leucine-aminopeptidase, and after mixing it with alpha 1-acid glycoprotein. The glycopeptide did not inhibit cell proliferation in kidney, submaxillary gland, or tongue epithelium. It seems to be the active component of a system that inhibits the proliferation of hepatocytes, probably by reducing their sensitivity to various mitogenic stimuli.
Institut Curie, Orsay, France.
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D000818:Animals; D000831:Animals, Newborn; D001798:Blood Proteins / Q000494:pharmacology; D002364:Caseins / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D006020:Glycopeptides / Q000097:blood / Q000494:pharmacology*; D006498:Hepatectomy; D007399:Interphase / Q000187:drug effects; D007668:Kidney / Q000166:cytology; D007931:Leucyl Aminopeptidase / Q000494:pharmacology; D008099:Liver / Q000166:cytology*; D008115:Liver Regeneration; D009961:Orosomucoid / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013363:Submandibular Gland / Q000166:cytology; D014059:Tongue / Q000166:cytology
D001798:Blood Proteins; D002364:Caseins; D006020:Glycopeptides; D009961:Orosomucoid; D007931:Leucyl Aminopeptidase