Abstract

Protein accumulation in liver cells contributes to alcohol‐induced hepatomegaly and is the result of an ethanol‐elicited deceleration of protein catabolism (Alcohol Clin Exp Res 1349, 1989). Because lysosomes are active in the degradation of most hepatic proteins, the present studies were conducted to determine whether ethanol administration altered the proteolytic activities of partially purified hepatic lysosomes. Rats were fed liquid diets containing either ethanol (36% of calories) or isocaloric maltodextrin for periods of 2–34 days. Prior to death, all animals were injected with [3H]leucine to label hepatic proteins. Rats subjected to even brief periods of ethanol feeding (2–8 days) exhibited significant hepatomegaly and hepatic protein accumulation compared with pair‐fed control animals. Crude liver homogenates and isolated lysosomal‐mitochondrial and cytosolic subfractions were incubated at 37°C, and the acid‐soluble radioactivity generated during incubation was measured as an index of proteolysis. At neutral pH, in vitro protein breakdown in incubated liver homogenates and subcellular fractions from control and ethanol‐fed rats did not differ significantly. The extent of protein hydrolysis increased when samples were incubated at pH 5.5, which approximates the pH optimum for catalysis by lysosomal acid proteases. Under the latter conditions, partially purified lysosomes from control animals had 2‐fold higher levels of proteolysis than corresponding fractions from ethanol‐fed rats. The difference in proteolytic capacity appeared to be related to a lower latency and a higher degree of fragility of lysosomes from ethanol‐fed rats at the acidic pH. The results suggest that ethanol‐induced alterations in lysosomal membranes may be partially responsible for their altered capacities for protein hydrolysis. Such changes may result from ethanol‐related alterations in lipid metabolism that may affect lysosome biogenesis or the maturation of lysosomes from autophagic vacuoles.

Original languageEnglish (US)
Pages (from-to)536-541
Number of pages6
JournalAlcoholism: Clinical and Experimental Research
Volume18
Issue number3
DOIs
StatePublished - Jun 1994

Keywords

  • Autophagic Vacuoles
  • Ethanol
  • Lysosomes
  • Proteolysis

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Toxicology
  • Psychiatry and Mental health

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