Effect of proteinase inhibitors on intracellular processing of cathepsin B, H and L in rat macrophages

Abstract

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.