Plasma protein catabolism in ethanol- and colchicine-treated liver slices.
The present study was conducted to determine whether the antisecretory agents colchicine and ethanol affect the intracellular degradation of plasma proteins in rat liver. Plasma proteins were prelabeled in vivo with [3H]leucine and their levels were monitored immunochemically in both the medium and extracts of rat liver slices incubated alone or in the presence of 50 microM colchicine or 25 mM ethanol. Compared with those left untreated, colchicine-treated slices had a 40-55% lower secretory capacity and, at one point, showed significant hepatocellular retention of total plasma proteins. Plasma protein secretion by ethanol-treated liver slices was 22-32% lower than controls, but there was no detectable retention of unsecreted plasma proteins in the ethanol-treated liver tissue. In all experiments, the total radioactivity in plasma proteins (i.e., the immunoprecipitable radioactivity in the liver plus that in the medium) decreased with time in a manner suggestive of intracellular degradation. Regression analyses of the rates of degradation of presecretory proteins revealed that compared with controls, plasma protein catabolism was accelerated 57% in colchicine-treated slices. In ethanol-treated liver slices, there was a 50% increase in the degradation of total plasma proteins and a 46% increase in albumin catabolism. In all cases, degradation was intracellular. These findings indicate that inhibition of hepatic protein secretion by either colchicine or ethanol is associated with accelerated catabolism of unsecreted plasma proteins, suggesting that hepatocellular degradative processes are responsive to changes in the levels of presecretory proteins and/or perturbations of the secretory process.
Donohue
T M
TM
Liver Study Unit, VA Medical Center, Omaha, Nebraska 68105.
Chaisson
M L
ML
Zetterman
R K
RK
D000818:Animals; D001798:Blood Proteins / Q000378:metabolism*; D003078:Colchicine / Q000633:toxicity*; D046508:Culture Techniques; D000431:Ethanol / Q000633:toxicity*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008657:Metabolic Clearance Rate / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains
D001798:Blood Proteins; D000431:Ethanol; D003078:Colchicine