Pathogenesis of alcohol-induced accumulation of protein in the liver.
Alcohol feeding to rats produced hepatomegaly, associated with enlargement of the hepatocytes. The increase in liver dry weight was accounted for not only by fat but also by protein accumulation, primarily in microsomes and cytosol, with a selective increase in export proteins: concentrations of both immunoreactive albumin and transferrin were augmented in liver microsomes and cytosol of ethanol-fed rats. To investigate the mechanism of this protein accumulation, [14C]leucine was injected intravenously and its incorporation into both liver and serum proteins was measured after various time intervals. Rates of synthesis and export were assessed from protein labeling and specific activities of leucyl-tRNA. Synthesis of liver protein and proalbumin were enhanced by chronic ethanol feeding, but this was not associated with a corresponding rise in serum albumin output. Actually, there was a significant retention of the label in liver albumin and transferrin with delayed appearance in the serum of ethanol-fed rats. This indicated that, regardless of the changes in synthesis, the export of protein from the liver into the plasma was impaired. This alteration in export was associated with a decreased amount of polymerized tubulin in the liver of ethanol-treated animals. Thus, both enhanced protein synthesis and defective export contribute to the ethanol-induced accumulation of liver protein, and the decrease in liver microtubules represents a possible site for impairment of protein export.
D000418:Albumins / Q000032:analysis; D000437:Alcoholism / Q000378:metabolism / Q000473:pathology; D000818:Animals; D000431:Ethanol / Q000633:toxicity*; D006529:Hepatomegaly / Q000139:chemically induced*; D006801:Humans; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008870:Microtubules / Q000032:analysis / Q000187:drug effects; D014176:Protein Biosynthesis; D011506:Proteins / Q000032:analysis / Q000378:metabolism*; D051381:Rats; D014168:Transferrin / Q000032:analysis
D000418:Albumins; D011506:Proteins; D014168:Transferrin; D000431:Ethanol