Effect of low-molecular-weight dextran on proteolytic and nonproteolytic lysosomal enzymes in isolated segments of rat proximal tubule.
Dextrans undergo glomerular filtration and are taken up by endocytosis into lysosomes of proximal tubule cells. We measured the activities of the intralysosomal proteolytic enzymes cathepsin B and L and the nonproteolytic acid phosphatase in microdissected segments of rat proximal tubules by means of fluorescent ultramicroassays. Cathepsin activities were increased following dextran injection in a dose-dependent manner. Cathepsin stimulation was not dextran-specific since enhanced proximal albumin uptake also increased cathepsin activities. Acid phosphatase remained almost unchanged. We conclude that increased proximal tubule uptake of macromolecules is accompanied by a rather specific stimulation of proteolytic enzymes in the lysosomes. For proteins this constitutes an adequate response to increased protein uptake to maintain the steady state between uptake and catabolism of proteins in lysosomes. For the nondigestible dextran the cathepsin induction is an inadequate response. Since lysosomal cathepsins are involved in breakdown of intracellular proteins, it is conceivable that the increased activities reflect increased cellular autophagy leading to proximal tubule damage.
Olbricht
C J
CJ
Abteilung Nephrologie, Medizinische Hochschule Hannover, BRD.
Irmler
H
H
Gutjahr
E
E
Koch
K M
KM
D000135:Acid Phosphatase / Q000378:metabolism; D000818:Animals; D002401:Cathepsin B / Q000378:metabolism; D056668:Cathepsin L; D002403:Cathepsins / Q000378:metabolism; D003546:Cysteine Endopeptidases; D003911:Dextrans / Q000737:chemistry / Q000494:pharmacology*; D010450:Endopeptidases; D004789:Enzyme Activation / Q000187:drug effects; D005260:Female; D066298:In Vitro Techniques; D007687:Kidney Tubules, Proximal / Q000187:drug effects* / Q000201:enzymology; D008247:Lysosomes / Q000187:drug effects / Q000201:enzymology; D008970:Molecular Weight; D051381:Rats; D017207:Rats, Sprague-Dawley
D003911:Dextrans; D000135:Acid Phosphatase; D002403:Cathepsins; D010450:Endopeptidases; D003546:Cysteine Endopeptidases; D002401:Cathepsin B; D056668:Cathepsin L; C534280:Ctsl protein, rat