Multicatalytic proteinase activity: age-related decline and protection from oxidative inactivation by HSP 90

B. Friguet, M. Conconi, L. I. Szweda, R. L. Levine, E. R. Stadtman

Research output: Contribution to journalArticle

Abstract

Modification of enzyme by oxidative processes and subsequent accumulation of altered protein have been implicated in age- and disease- related impairment of cellular function. The multicatalytic proteinase (MCP). a multienzymatic proteolytic complex is believed to play a key role in the degradation of damaged protein and consequently to be very important in the level of altered protein in the cell. The MCP has been purified to apparent homogeneity from the liver of young (8 month) and old (24 month) Fisher 344 rats. Of three MCP activities that can be assayed using fluorogenic substrates: trypsin-like, chymotrypsin-like and peptidylglutamyl-peptide hydrolase, only the latter was found to decline with age to a value approximately 50% of that observed for protease purified from 8 month old rats. The purified preparations were then exposed to a metal catalyzed oxidation system as a mimic of oxidative damage. Both trypsin-like and peptidylglutamyl-peptide hydrolase are sensitive to metal catalyzed oxidation. However, in the presence of a 95 kDa copurifying protein, the trypsin-like activity is protected against oxidation in both old and young enzyme preparations. This 95 kDa protein has been identified as Hsp 90. Addition of purified Hsp 90 to pure MCP has been found to protect trypsin-like activity from oxidative inactivation. These results may have important implications in age dependent build up of damaged protein.

Original languageEnglish (US)
Pages (from-to)A1402
JournalFASEB Journal
Volume10
Issue number6
StatePublished - Dec 1 1996

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

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