Distribution of cathepsins B and L in the kidney and their role in tubular protein absorption.
Intralysosomal proteinase activity, due to cathepsins B and L, was measured in microdissected segments of rat nephron, using Z-Phen-Arg-7-amido-4-methylcoumarin as the substrate. Cathepsin B was determined with Z-Arg-Arg-7-amido-4-methylcoumarin. The enzymes cleave on the carboxy side of arginine and release free 7-amino-4-methylcoumarin, which is highly fluorescent and can be measured at very low concentrations in small volumes. Enzyme activities were measured in three individual microdissected segments of the proximal tubule and in six different segments of the distal tubule. Experiments were performed in normal non-proteinuric rats and in several rat models of glomerular proteinuria. The distributions of cathepsin activities along the nephron were similar. In all groups, the convoluted part of the proximal tubule had enzyme activities three times higher than in the remaining segments of the nephron. In the last millimeter of the pars convoluta and in the pars recta of the proximal tubule, enzyme activities were two to three times higher in proteinuric animals. These findings suggest that in proteinuric animals the increase in the protein load delivered to the proximal tubules selectively stimulated cathepsin B and L activities in the last millimeter of the pars convoluta and in the pars recta of the proximal tubule, presumably because of an increase in protein uptake, and that cathepsins B and L participate in lysosomal digestion of protein reabsorbed from the glomerular ultrafiltrate via endocytosis.
Olbricht
C J
CJ
Abteilung Nephrologie, Medizinische Hochschule Hannover, Germany.
D000042:Absorption; D000818:Animals; D002401:Cathepsin B / Q000378:metabolism / Q000502:physiology*; D056668:Cathepsin L; D002403:Cathepsins / Q000378:metabolism / Q000502:physiology*; D003546:Cysteine Endopeptidases / Q000378:metabolism / Q000502:physiology; D010450:Endopeptidases; D005260:Female; D007668:Kidney / Q000201:enzymology* / Q000502:physiology; D007684:Kidney Tubules / Q000201:enzymology / Q000378:metabolism*; D009399:Nephrons / Q000201:enzymology; D011506:Proteins / Q000378:metabolism*; D051381:Rats; D014018:Tissue Distribution
D011506:Proteins; D002403:Cathepsins; D010450:Endopeptidases; D003546:Cysteine Endopeptidases; D002401:Cathepsin B; D056668:Cathepsin L; C534280:Ctsl protein, rat