Inactivation of the proteasome by 4-hydroxy-2-nonenal is site specific and dependant on 20S proteasome subtypes

Luc Farout, Jean Mary, Joëlle Vinh, Luke I. Szweda, Bertrand Friguet

Research output: Contribution to journalArticle

100 Citations (Scopus)

Abstract

The proteasome represents a major intracellular proteolytic system responsible for the degradation of oxidized and ubiquitinated proteins in both the nucleus and cytoplasm. We have previously reported that proteasome undergoes modification by the lipid peroxidation product 4-hydroxy-2-nonenal (HNE) and exhibits declines in peptidase activities during cardiac ischemia/reperfusion. This study was undertaken to characterize the effects of HNE on the structure and function of the 20S proteasome. To assess potential tissue-specific differences in the response to HNE, we utilized purified 20S proteasome from heart and liver, tissues that express different proteasome subtypes. Following incubation of heart and liver 20S proteasome with HNE, changes in the 2D gel electrophoresis patterns and peptidase activities of the proteasome were evaluated. Proteasome subunits were identified by mass spectrometry prior to and following treatment with HNE. Our results demonstrate that specific subunits of the 20S proteasome are targeted for modification by HNE and that modified proteasome exhibits selective alterations in peptidase activities. The results provide evidence for a likely mechanism of proteasome inactivation in response to oxidative stress particularly during cardiac ischemia/reperfusion.

Original languageEnglish (US)
Pages (from-to)133-140
Number of pages8
JournalArchives of Biochemistry and Biophysics
Volume453
Issue number1
DOIs
StatePublished - Sep 1 2006

Fingerprint

Proteasome Endopeptidase Complex
Peptide Hydrolases
Liver
Reperfusion
4-hydroxy-2-nonenal
Ischemia
Ubiquitinated Proteins
Tissue
Oxidative stress
Electrophoresis, Gel, Two-Dimensional
Electrophoresis
Lipid Peroxidation
Mass spectrometry
Mass Spectrometry
Cytoplasm
Oxidative Stress
Gels
Lipids
Degradation

Keywords

  • 4-Hydroxy-2-nonenal
  • Heart
  • Liver
  • Mass spectrometry
  • Oxidative stress
  • Oxidatively modified proteins
  • Proteasome

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology

Cite this

Inactivation of the proteasome by 4-hydroxy-2-nonenal is site specific and dependant on 20S proteasome subtypes. / Farout, Luc; Mary, Jean; Vinh, Joëlle; Szweda, Luke I.; Friguet, Bertrand.

In: Archives of Biochemistry and Biophysics, Vol. 453, No. 1, 01.09.2006, p. 133-140.

Research output: Contribution to journalArticle

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