Comparative effects of acute ethanol dosage on liver and muscle protein metabolism

Experiments were performed to address some outstanding issues and investiga te possible mechanisms relating to the acute comparative effects of ethanol on liver and skeletal muscle protein metabolism. Ethanol (EtOH) treated ra ts were injected (i.p.) with a bolus of EtOH (75 mmol/kg body weight) and s acrificed at 20 min, 1-, 2.5-, 6-, and 24-hr time points. Control rats were injected with saline (Con-Sal; 0.15 mmol/L NaCl). All 24-hr ethanol-treate d animals were compared with saline-injected rats subjected to controlled f eeding (i.e. pair-fed controls for 24 hr EtOH). At 24 hr, there was no meas urable alcohol in the plasma, whereas high levels were seen from 20 min to 6 hr (up to 448 mg/dL). Plasma levels of albumin were reduced at initial ti me points, and activities of aspartate aminotransferase increased, but ther e was no histological, evidence of overt tissue damage either in muscle or liver. Hepatic protein and RNA contents and indices of tissue (C-s and k(s) ) and whole-body (V-s) protein synthesis were significantly increased in et hanol-dosed rats relative to saline-injected pair-fed controls at 24 hr. In the liver, four of the seven cytoplasmic proteases investigated (alanyl-, arginyl-, and pyroglutamyl-aminopeptidases and proline-endopeptidase) showe d significant increases in activity at 24 hr relative to pair-fed controls; four of the six lysosomal proteases showed significant decreases in activi ty (dipeptidyl-aminopeptidase II and cathepsins B, L, and H). In skeletal m uscle, k(s) fell progressively between I and 24 hr (-25 to -69%; P < 0.001) , but no significant changes in skeletal muscle protease activities were se en at 24 hr. At 24 hr after ethanol dosage in vivo, there were no significa nt increases in protein carbonyl content in liver or skeletal muscle compar ed to pair-fed controls (muscle levels actually decreased slightly). Howeve r, using either rat or human tissue, both liver and muscle carbonyl increas ed in vitro in response to superoxide and hydroxyl radicals: muscle was mor e susceptible to carbonyl formation than liver and both tissues were more s ensitive to hydroxyl compared to superoxide radicals. These results show di vergent effects of acute ethanol treatment on liver and skeletal muscle pro tein metabolism which may not be linked to in vivo free radical-mediated pr otein damage (as indicated by carbonyl formation), at least in the short te rm. BIOCHEM PHARMACOL 60;12:1773-1785, 2000. (C) 2000 Elsevier Science Inc.