Cathepsin-D-dependent initiation of the hydrolysis by lysosomal enzymes of apoprotein B from low-density lipoproteins.
The degradation of 135I-apoprotein B of human low-density lipoprotein by cell extracts of cultured bovine aortic smooth muscle cells was determined by measuring the formation of acid-soluble products and by analyzing the electrophoretic patterns of digested apoprotein in gels containing sodium dodecyl sulfate. Degradation resulted in an initial rapid accumulation of a limited number of distinct smaller fragments. Two products with apparent molecular weights of 220,000 and 200,000 predominated. Pepstatin inhibited proteolysis almost completely, as measured by either assay. Leupeptin decreased hydrolysis to acid-soluble products by approximately 50%, but had no effect on the initial cleavage of intact apoprotein B. Similar results were found in the case of extracts from cultured human skin fibroblasts and from adult bovine arterial smooth muscle. Leupeptin inhibited intracellular degradation of 125I-apoprotein B in cultured cells by approximately 50%. It is concluded that the intralysosomal degradation of apoprotein B involves an initial limited endoproteolytic attack at susceptible sites by cathepsin D. This and other enzymes, including cathepsin B, then act synergistically to bring degradation to completion.
D000818:Animals; D001011:Aorta / Q000378:metabolism; D001053:Apolipoproteins / Q000378:metabolism*; D001055:Apolipoproteins B; D002402:Cathepsin D; D002403:Cathepsins / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D002417:Cattle; D002478:Cells, Cultured; D006801:Humans; D006868:Hydrolysis; D007976:Leupeptins / Q000494:pharmacology; D008077:Lipoproteins, LDL / Q000378:metabolism*; D008247:Lysosomes / Q000201:enzymology; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism*; D010436:Pepstatins / Q000494:pharmacology
D001053:Apolipoproteins; D001055:Apolipoproteins B; D007976:Leupeptins; D008077:Lipoproteins, LDL; D010436:Pepstatins; D002403:Cathepsins; D002402:Cathepsin D