Abstract
Administration of Ep459-asialofetuin conjugate (Ep459-AF) and pepstatin-asialofetuin conjugate (Ps-AF) to rats effectively inhibited lysosomal BANA hydrolase and cathepsin D in the liver, respectively, at a very low dose. Ep459-AF treatment also led to an accumulation of autolysosomes in rat liver. There was a close correlation between the accumulation of autolysosomes and the inhibition of BANA hydrolase activity. However, as opposed to the inhibition of thiol proteases, the inhibition of cathepsin D did not cause accumulation of autolysosomes in the rat liver. These results suggest that autophagy in rat hepatocytes is a common occurrence under normal physiological conditions and that thiol proteases are digestive enzymes essential for the autolysomes.
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