Comparative effects of acute ethanol dosage on liver and muscle protein metabolism.
Experiments were performed to address some outstanding issues and investigate possible mechanisms relating to the acute comparative effects of ethanol on liver and skeletal muscle protein metabolism. Ethanol (EtOH)-treated rats were injected (i.p.) with a bolus of EtOH (75 mmol/kg body weight) and sacrificed 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-treated animals were compared with saline-injected rats subjected to controlled feeding (i.e. pair-fed controls for 24 hr EtOH). At 24 hr, there was no measurable 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 time points, and activities of aspartate aminotransferase increased, but there 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 ethanol-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) showed significant increases in activity at 24 hr relative to pair-fed controls; four of the six lysosomal proteases showed significant decreases in activity (dipeptidyl-aminopeptidase II and cathepsins B, L, and H). In skeletal muscle, k(s) fell progressively between 1 and 24 hr (-25 to -69%; P < 0.001), but no significant changes in skeletal muscle protease activities were seen at 24 hr. At 24 hr after ethanol dosage in vivo, there were no significant increases in protein carbonyl content in liver or skeletal muscle compared to pair-fed controls (muscle levels actually decreased slightly). However, using either rat or human tissue, both liver and muscle carbonyl increased in vitro in response to superoxide and hydroxyl radicals: muscle was more susceptible to carbonyl formation than liver and both tissues were more sensitive to hydroxyl compared to superoxide radicals. These results show divergent effects of acute ethanol treatment on liver and skeletal muscle protein metabolism, which may not be linked to in vivo free radical-mediated protein damage (as indicated by carbonyl formation), at least in the short term.
Reilly
M E
ME
Department of Clinical Biochemistry, King's College School of Medicine, SE5 9PJ, London, UK.
Mantle
D
D
Salisbury
J
J
Peters
T J
TJ
Preedy
V R
VR
D000210:Acute-Phase Reaction; D000818:Animals; D002492:Central Nervous System Depressants / Q000008:administration & dosage / Q000494:pharmacology; D010450:Endopeptidases / Q000378:metabolism; D000431:Ethanol / Q000008:administration & dosage* / Q000494:pharmacology; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D009124:Muscle Proteins / Q000096:biosynthesis / Q000187:drug effects; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D009929:Organ Size / Q000187:drug effects; D010949:Plasma / Q000737:chemistry; D051381:Rats; D017208:Rats, Wistar
D002492:Central Nervous System Depressants; D009124:Muscle Proteins; D000431:Ethanol; D010450:Endopeptidases