Rat serum factors inhibiting the G1-S transition in hepatocytes. I. Production of a low molecular weight inhibitor by proteases or liver fractions.
An attempt was made to detect the serum factors inhibiting the G1-S transition in synchronized, baby rat hepatocytes. In untreated adult rat serum, this inhibitory activity was always linked to high molecular weight (HMW) compounds. Incubation of serum with trypsin or chymotrypsin resulted in the formation of a low molecular weight (LMW) G1-S inhibitory factor. The same result was obtained with fractions from adult rat liver but not with kidney or spleen fractions. Separation of the LMW factor by ultrafiltration increased its specific activity by about 10(3). The active period in the cell cycle of both the LMW and HMW factors was the same: the late G1 phase. However, the activity of the LMW factor was not blocked by the Kunitz factor. An enzymatic transformation of the HMW factor might be induced by liver cell membrane-bound proteases and constitute a mechanism regulating hepatocyte proliferation.
D000818:Animals; D002918:Chymotrypsin / Q000494:pharmacology; D006131:Growth Inhibitors / Q000097:blood*; D007399:Interphase; D007668:Kidney; D008099:Liver / Q000166:cytology*; D008970:Molecular Weight; D051381:Rats; D013154:Spleen; D014357:Trypsin / Q000494:pharmacology; D014360:Trypsin Inhibitor, Kunitz Soybean / Q000494:pharmacology
D006131:Growth Inhibitors; D014360:Trypsin Inhibitor, Kunitz Soybean; D002918:Chymotrypsin; D014357:Trypsin