Effect of proteinase inhibitors on intracellular processing of cathepsin B, H and L in rat macrophages.
The effects of various proteinase inhibitors on the processing of lysosomal cathepsins B, H and L were investigated in cultured rat peritoneal macrophages. The processing of newly synthesized pro-cathepsins B, H and L to the mature single-chain enzymes was sensitive to a metal chelator,1,10-phenanthroline, and a synthetic metalloendopeptidase substrate, Z-Gly-Leu-NH2, and insensitive to inhibitors of serine proteinases, aspartic proteinases and cysteine proteinases. Inhibitors of cysteine proteinases, E-64-d and leupeptin, inhibited the processing of the single-chain forms of cathepsins B, H and L to the two-chain forms. These results suggest that (a) metal endopeptidase(s) is (are) involved in the propeptide processing of cathepsin B, H and L, and that proteolytic cleavages of the mature single-chain cathepsins are accomplished by cysteine proteinases in lysosomes.
Hara
K
K
Division of Enzyme Chemistry, University of Tokushima, Japan.
Kominami
E
E
Katunuma
N
N
D000818:Animals; D002401:Cathepsin B / Q000235:genetics; D056655:Cathepsin H; D056668:Cathepsin L; D002403:Cathepsins / Q000235:genetics*; D002478:Cells, Cultured; D003546:Cysteine Endopeptidases; D010450:Endopeptidases; D007700:Kinetics; D008264:Macrophages / Q000187:drug effects / Q000201:enzymology*; D011480:Protease Inhibitors / Q000494:pharmacology*; D011499:Protein Processing, Post-Translational / Q000187:drug effects*; D051381:Rats
D011480:Protease Inhibitors; D002403:Cathepsins; D010450:Endopeptidases; D003546:Cysteine Endopeptidases; D002401:Cathepsin B; D056668:Cathepsin L; C534280:Ctsl protein, rat; D056655:Cathepsin H; C534128:Ctsh protein, rat