Translocation of epidermal growth factor to the hepatocyte nucleus during rat liver regeneration.
To determine the fate of exogenous epidermal growth factor (EGF) in regenerating liver, 125I-labeled EGF was injected into rat portal veins at various times after 70% hepatectomy. Epidermal growth factor was taken up by the liver remnant at all time points studied (0, 4, 8, 16, and 36 h), but at 8 h after hepatectomy a large quantity was retained by the liver and EGF degradation products appearing in the bile decreased markedly. Electron microscopic autoradiography of the regenerating livers 1 h after injection of 125I-EGF demonstrated that 27% of the grains were associated with hepatocyte nuclei compared to 0.5% in shamoperated controls. There was also a concomitant decrease in grains associated with the lysosomal compartment. Nuclei isolated from regenerating livers exposed to 125I-EGF also demonstrated a three-fold increase in radioactivity compared to nuclei from control livers. Nearly 70% of nuclear radioactivity was precipitable with a specific antibody to EGF, and a small fraction appeared to be part of a high molecular weight complex. These data support the hypothesis that during the pre-S phase of liver regeneration, EGF is translocated to the nucleus rather than to lysosomes, and may participate in the initiation of deoxyribonucleic acid synthesis or alteration of gene expression.
D000818:Animals; D001646:Bile / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism / Q000648:ultrastructure; D004815:Epidermal Growth Factor / Q000378:metabolism*; D006498:Hepatectomy; D007457:Iodine Radioisotopes; D008099:Liver / Q000166:cytology* / Q000378:metabolism / Q000648:ultrastructure; D008115:Liver Regeneration; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains
D007457:Iodine Radioisotopes; D004815:Epidermal Growth Factor