title: Inactivation of lysosomal proteases by oxidized low density lipoprotein is partially responsible for its poor degradation by mouse peritoneal macrophages.
abstract: Deficient processing of apo B in oxidized LDL (ox-LDL) by macrophage lysosomal proteases has been documented and attributed to modifications in apo B. We have investigated whether direct inactivation of lysosomal proteases by ox-LDL could also be responsible for this deficient degradation. When mouse peritoneal macrophages (MPM) were preincubated for 21 h at 37 degrees C with ox-LDL, LDL, or vortex-aggregated LDL, only ox-LDL inhibited the subsequent degradation of 125I-labeled forms of the above lipoproteins. Uptake of labeled lipoproteins was not appreciably affected by preincubation with ox-LDL, suggesting that the inhibition was at the level of lysosomal degradation. Thiol protease activity of cell extracts at pH 4.0, was reduced in MPM preincubated with ox-LDL relative to cells preincubated with LDL or medium alone. Extracts from untreated MPM, or mixtures of cathepsin B and D, showed a reduced ability to degrade 125I-LDL at pH 4.5 and reduced cathepsin B activity, after incubation with ox-LDL relative to incubation with LDL. Thus, the reduced degradation of lipoproteins in MPM pretreated with ox-LDL could be due to direct inactivation of the lysosomal protease, cathepsin B.
authors.affiliation: Department of Cell Biology, Cleveland Clinic Foundation, Ohio 44195.
authors.forename: G
authors.initials: G
authors.lastname: Hoppe
authors.forename: J
authors.initials: J
authors.lastname: O'Neil
authors.forename: H F
authors.initials: HF
authors.lastname: Hoff
mesh_terms: D000818:Animals; D002401:Cathepsin B / Q000037:antagonists & inhibitors*; D002402:Cathepsin D / Q000037:antagonists & inhibitors*; D002478:Cells, Cultured; D005260:Female; D008077:Lipoproteins, LDL / Q000378:metabolism* / Q000494:pharmacology; D008247:Lysosomes / Q000201:enzymology*; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D010084:Oxidation-Reduction
chemical_list: D008077:Lipoproteins, LDL; D002401:Cathepsin B; D002402:Cathepsin D