Cathepsin B and L in isolated proximal tubular segments during acute and chronic proteinuria.
Acute and chronic proteinuria were studied in rats, using lysosomal cathepsin B and L as marker enzymes for tubular protein degradation. The activity of cathepsin B and L has been determined in microdissected segments S1, S2 and S3 of the proximal tubule by an ultramicroassay. Z-Phenylalanyl-arginine-7-amido-4-methylcoumarin served as a substrate. In normoproteinuric Sprague-Dawley rats, induction of acute unselective glomerular proteinuria with Adriamycin (5 mg/kg body weight) revealed a moderate activity increase of cathepsin B and L in the S2 segment, reaching 12.6 +/- 5.6 versus 8.6 +/- 4.2 pmol.mm-1.min-1 in controls. In contrast, Munich Wistar Frömter (MWF) rats, that are characterized by a genetically determined, chronically elevated glomerular protein excretion, showed a very high activity of cathepsin selectively in S2 of 25.0 +/- 12.1 pmol.mm-1.min-1. Acute proteinuria induced by Adriamycin in chronic proteinuric MWF rats could increase cathepsin activity in the S3 segment only, showing 12.0 +/- 8.3 versus 6.8 +/- 4.0 pmol.mm-1.min-1 in MWF control rats. In conclusion, chronically increased protein filtration changes the functional reserve capacity of the proximal tubule. While acutely induced glomerular proteinuria in normoproteinuric rats stimulates lysosomal proteolytic activity mainly in S2 segment, chronic proteinuric MWF rats may display already a maximally stimulated cathepsin activity in this segment probably due to long-term increased tubular protein load. In case of acute elevation of chronic proteinuria, the consecutive S3 segment shows increased lysosomal function for protein conservation.
Eisenberger
U
U
Department of Internal Medicine, Hannover Medical School, Germany.
Fels
L M
LM
Olbricht
C J
CJ
Stolte
H
H
D000208:Acute Disease; D000818:Animals; D002401:Cathepsin B / Q000378:metabolism*; D056668:Cathepsin L; D002403:Cathepsins / Q000378:metabolism*; D002908:Chronic Disease; D003404:Creatinine / Q000652:urine; D003546:Cysteine Endopeptidases; D004317:Doxorubicin; D010450:Endopeptidases; D005260:Female; D007687:Kidney Tubules, Proximal / Q000201:enzymology*; D009401:Nephrosis / Q000139:chemically induced / Q000378:metabolism; D011507:Proteinuria / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D011920:Rats, Inbred WF; D017207:Rats, Sprague-Dawley
D004317:Doxorubicin; D003404:Creatinine; D002403:Cathepsins; D010450:Endopeptidases; D003546:Cysteine Endopeptidases; D002401:Cathepsin B; D056668:Cathepsin L; C534280:Ctsl protein, rat