Simultaneous isolation of human kidney cathepsins B, H, L and C and their characterisation

J Chromatogr B Biomed Appl. 1996 Jun 7;681(2):251-62. doi: 10.1016/0378-4347(95)00555-2.

Abstract

A procedure for the simultaneous isolation of four cysteine proteinases, cathepsins B, H, L and C, from human kidney is described. The method includes concentration of the acidified homogenate by ammonium sulphate precipitation. The resuspended and dialysed precipitate was chromatographed on DEAE-cellulose DE-32, to allow separation of cathepsins H and C from cathepsins B and L. The main isoform of cathepsin H was separated from cathepsin C by cation-exchange chromatography on CM-Sephadex C-50. These two enzymes were further purified by covalent chromatography on thiopropyl Sepharose and gel permeation on Sephacryl S-200. The last step allowed separation of cathepsin C and the minor isoform of cathepsin H. Purification of the other two enzymes, cathepsins B and L, was carried out on thiol Sepharose, followed by chromatography on CM-Sepharose C-50. In this step, pure cathepsin L was obtained, while two isoforms of cathepsin B had to be finally purified on Sephacryl S-200 columns. The purity of each enzyme was analysed by sodium dodecyl sulphate polyacrylamide gel electrophoresis, isoelectric focusing on polyacrylamide gels and N-terminal sequencing. The activities of the purified cathepsins B, H and L were determined in terms of kcat/KM for three substrates, Z-Phe-Arg-MCA, Z-Arg-Arg-MCA and Arg-MCA. The method produced 25 mg of cathepsin B, 6.5 mg of cathepsin H, 1.5 mg of cathepsin L and 3.8 mg of cathepsin C from 3.5 kg of human kidney.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Cathepsin B / chemistry
  • Cathepsin B / isolation & purification*
  • Cathepsin C
  • Cathepsin H
  • Cathepsin L
  • Cathepsins / chemistry
  • Cathepsins / isolation & purification*
  • Cations
  • Chromatography, Ion Exchange
  • Cysteine Endopeptidases*
  • Dipeptidyl-Peptidases and Tripeptidyl-Peptidases / chemistry
  • Dipeptidyl-Peptidases and Tripeptidyl-Peptidases / isolation & purification*
  • Electrophoresis, Polyacrylamide Gel
  • Endopeptidases*
  • Humans
  • Isoelectric Focusing
  • Kidney / enzymology*
  • Peptide Fragments / chemistry
  • Sequence Analysis

Substances

  • Cations
  • Peptide Fragments
  • Cathepsins
  • Endopeptidases
  • Dipeptidyl-Peptidases and Tripeptidyl-Peptidases
  • Cathepsin C
  • Cysteine Endopeptidases
  • Cathepsin B
  • CTSL protein, human
  • Cathepsin L
  • CTSH protein, human
  • Cathepsin H