Activities of cathepsins B and L in isolated nephron segments from proteinuric and nonproteinuric rats.
The intralysosomal proteinases cathepsins B and L were measured in microdissected segments of rat nephron. Z-Arg-Arg-NMec served as the substrate for cathepsin B and Z-Phe-Arg-NMec for cathepsin B and L together. Individual S1, S2, and S3 segments of proximal tubules, TDL, MTAL, CTAL, DCT, CCD, and OMCD were dissected from young female rats weighing 130 +/- 11 g with low protein excretion (0.68 +/- 0.1 mg/24 h), from older female rats weighing 289 +/- 9 g with protein excretion of 10 +/- 6.3 mg/24 h, from older male rats weighing 404 +/- 11 g with protein excretion of 22 +/- 6 mg/24 h, from female rats weighing 198 +/- 10 g with albumin-induced proteinuria (411 +/- 134 mg/24 h), and from female rats weighing 203 +/- 11 g with low protein excretion (2.7 +/- 0.4 mg/24 h). The distributions of cathepsin activities along the nephron were similar. In all five groups, S1 and S2 segments had enzyme activities three times higher than in all remaining segments. In S2 and S3, 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 activities in the S2 and S3 segments, presumably because of an increase in protein uptake, and that cathepsins B and L participate in lysosomal digestion of protein reabsorbed from the glomerular filtrate via endocytosis.
D000375:Aging; D000818:Animals; D002401:Cathepsin B; D056668:Cathepsin L; D002403:Cathepsins / Q000378:metabolism*; D003374:Coumarins / Q000096:biosynthesis; D003546:Cysteine Endopeptidases; D010450:Endopeptidases; D005260:Female; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D009399:Nephrons / Q000378:metabolism* / Q000473:pathology; D011480:Protease Inhibitors / Q000494:pharmacology; D011507:Proteinuria / Q000139:chemically induced / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values; D012710:Serum Albumin, Bovine / Q000494:pharmacology; D012727:Sex Characteristics; D013997:Time Factors
D003374:Coumarins; D011480:Protease Inhibitors; D012710:Serum Albumin, Bovine; D002403:Cathepsins; D010450:Endopeptidases; D003546:Cysteine Endopeptidases; D002401:Cathepsin B; D056668:Cathepsin L; C534280:Ctsl protein, rat; C028743:7-amino-4-methylcoumarin