Age-related decline of rat liver multicatalytic proteinase activity and protection from oxidative inactivation by heat-shock protein 90

Mariangela Conconi, Luke I. Szweda, Rodney L. Levine, Earl R. Stadtman, Bertrand Friguet

Research output: Contribution to journalArticle

174 Scopus citations

Abstract

To test whether an observed age-related increased in the level of oxidized protein in rat liver is due to a decrease in the activity of the multicatalytic proteinase (MCP), this protease was isolated from liver of young (8-month-old) and old (24-month-old) male Fischer 344 rats. Three peptidase activities of the MCP were assayed using fluorogenic peptides: trypsin-like, chymotrypsin-like, and peptidylglutamyl-peptide hydrolase. Only peptidylglutamyl-peptide hydrolase activity declined with age, with protease from old animals exhibiting approximately 50% of the activity of that from young animals. Bidimensional gel electrophoresis and thermostability studies did not reveal age-related structural modifications of the MCP subunits. Peptidylglutamyl-peptide hydrolase activity and trypsin-like activity were sensitive to metal-catalyzed oxidation. In some preparations, a 95-kDa protein that has been identified as the heat shock protein 90 copurified with the MCP. In the presence of HSP 90, trypsin-like activity is protected from oxidative inactivation and chymotrypsin-like activity is slightly activated. Peptidylglutamyl-peptide hydrolase activity remained sensitive to oxidation in protease isolated from young rats, but that from old rats was resistant to oxidative inactivation. Furthermore, addition of rat HSP 90 to rat liver MCP (purified from 8-month-old animals and free of contaminating HSP 90) was found to protect trypsin-like activity from oxidative inactivation.

Original languageEnglish (US)
Pages (from-to)232-240
Number of pages9
JournalArchives of Biochemistry and Biophysics
Volume331
Issue number2
DOIs
StatePublished - Jul 15 1996

Keywords

  • Aging
  • heat shock protein 90
  • multicatalytic proteinase
  • oxidative inactivation
  • rat liver

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology

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