A proteolytic activity enhanced by arsenite in Chinese hamster ovary cells: possible involvement in arsenite-induced cell killing

Biochem Biophys Res Commun. 1994 Jul 29;202(2):1015-22. doi: 10.1006/bbrc.1994.2030.

Abstract

Treatment of Chinese hamster ovary (CHO-K1) cells with 10 microM sodium arsenite for 24 h resulted in enhancement of a proteolytic activity toward the chromogenic substrate CBZ-Phe-Arg-AMC. Presence of dithiothreitol and a pH between 4 and 6 were required for displaying its full hydrolytic activity. According to its substrate- and inhibitor-specificity, this arsenite-induced proteolytic activity was very similar to lysosomal cathepsin B. Arsenite cytotoxicity was further shown to be partially prevented by inhibitors that inhibited the arsenite-induced protease, such as antipain and chymostatin, but not by protease inhibitors without inhibitory effects on the arsenite-induced protease. Our present results suggest that the arsenite-induced protease activity may be involved in arsenite's killing effects.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arsenites / pharmacology*
  • CHO Cells / drug effects
  • CHO Cells / enzymology*
  • Cell Death / drug effects*
  • Coumarins / metabolism
  • Cricetinae
  • Dipeptides / metabolism
  • Dithiothreitol / pharmacology
  • Endopeptidases / metabolism*
  • Fluorescent Dyes
  • Hydrogen-Ion Concentration
  • Molecular Weight
  • Protease Inhibitors / pharmacology
  • Sodium Compounds / pharmacology*
  • Substrate Specificity

Substances

  • Arsenites
  • Coumarins
  • Dipeptides
  • Fluorescent Dyes
  • Protease Inhibitors
  • Sodium Compounds
  • sodium arsenite
  • benzyloxycarbonyl-phenylalanylarginine-4-methylcoumaryl-7-amide
  • Endopeptidases
  • Dithiothreitol