Ethanol Administration Alters the Proteolytic Activity of Hepatic Lysosomes

作者：Terrence M. Donohue, Daniel L. McVicker, Kusum K. Kharbanda, Mary L. Chaisson, Rowen K. Zetterman · 发表于：Alcoholism Clinical and Experimental Research · 年份：1994 · DOI：10.1111/j.1530-0277.1994.tb00906.x · 被引用次数：58 · 研究领域：Lipid metabolism and biosynthesis、Diet, Metabolism, and Disease、Natural Antidiabetic Agents Studies

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 13:49, 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 degrees 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 ...