The potential role of human kidney cortex cysteine proteinases in glomerular basement membrane degradation.
(1) The degradation of glomerular basement membrane and some of its constituent macromolecules by human kidney lysosomal cysteine proteinases has been investigated. Three cysteine proteinases were extracted from human renal cortex and purified to apparent homogeneity. These proteinases were identified as cathepsins B, H and L principally by their specific activities towards Z-Arg-Arg-NHMec, Leu-NNap and Z-Phe-Arg-NHMec, respectively, and their Mr on SDS-polyacrylamide gel electrophoresis under reducing conditions. (2) Cathepsins B and L, at acid pH, readily hydrolysed azocasein and degraded both soluble and basement membrane type IV and V collagen, laminin and proteoglycans. Their action on the collagens was temperature-dependent, suggesting that they are only active towards denatured collagen. Cathepsin L was more active in degrading basement membrane collagens than was cathepsin B but qualitatively the action of both proteinases were similar, i.e., at below 32 degrees C the release of an Mr 400,000 hydroxyproline product which at 37 degrees C was readily hydrolysed to small peptides. (3) In contrast, cathepsin H had no action on soluble or insoluble collagens or laminin but did, however, hydrolyse the protein core of 35S-labelled glomerular heparan sulphate-rich proteoglycan. (4) Thus renal cysteine proteinases form a family of enzymes which together are capable of degrading the major macromolecules of the glomerular extracellular matrix.
Thomas
G J
GJ
K.R.U.F. Institute of Renal Disease, University of Wales College of Medicine, Cardiff, U.K.
Davies
M
M
D001485:Basement Membrane / Q000201:enzymology / Q000378:metabolism; D002403:Cathepsins / Q000502:physiology; D003094:Collagen / Q000378:metabolism; D003546:Cysteine Endopeptidases / Q000302:isolation & purification / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D007672:Kidney Cortex / Q000201:enzymology* / Q000502:physiology; D007678:Kidney Glomerulus / Q000201:enzymology / Q000378:metabolism*; D007797:Laminin / Q000378:metabolism; D011257:Pregnancy Proteins / Q000378:metabolism; D011509:Proteoglycans / Q000378:metabolism; D012995:Solubility
D007797:Laminin; D011257:Pregnancy Proteins; D011509:Proteoglycans; D003094:Collagen; D002403:Cathepsins; D003546:Cysteine Endopeptidases