Decreased enzyme activities of chaperones PDI and BiP in aged mouse livers

Jonathan E. Nuss, Kashyap B. Choksi, James H. DeFord, John Papaconstantinou

Research output: Contribution to journalArticle

80 Citations (Scopus)

Abstract

The endoplasmic reticulum (ER) is a target for endogenously generated reactive oxygen species (ROS) during aging. We have previously shown that the ER chaperones, protein disulfide isomerase (PDI) and immunoglobulin heavy chain binding protein (BiP), are oxidatively modified within the livers of aged mice. In this study we assess the functional consequences of the age-dependent oxidation of these two proteins. Specific activity measurements, performed on purified protein samples obtained from young and aged mouse livers, show definitive decreases in BiP ATPase activity and dramatic reductions in PDI enzymatic activity with age. Overall, these results suggest that protein folding and other activities mediated through PDI and BiP are diminished during aging. Furthermore, the relative loss of these chaperone-like activities could directly contribute to the age-dependent accumulation of misfolded proteins, a characteristic of the aging phenotype.

Original languageEnglish (US)
Pages (from-to)355-361
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume365
Issue number2
DOIs
StatePublished - Jan 11 2008

Fingerprint

Protein Disulfide-Isomerases
Enzyme activity
Liver
Carrier Proteins
Aging of materials
Endoplasmic Reticulum
Enzymes
Protein folding
Proteins
Protein Folding
Adenosine Triphosphatases
Reactive Oxygen Species
Phenotype
Oxidation

Keywords

  • Aging
  • BiP
  • Carbonylation
  • Chaperone modification
  • Oxidative stress
  • PDI
  • Protein folding

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

Cite this

Decreased enzyme activities of chaperones PDI and BiP in aged mouse livers. / Nuss, Jonathan E.; Choksi, Kashyap B.; DeFord, James H.; Papaconstantinou, John.

In: Biochemical and Biophysical Research Communications, Vol. 365, No. 2, 11.01.2008, p. 355-361.

Research output: Contribution to journalArticle

Nuss, Jonathan E. ; Choksi, Kashyap B. ; DeFord, James H. ; Papaconstantinou, John. / Decreased enzyme activities of chaperones PDI and BiP in aged mouse livers. In: Biochemical and Biophysical Research Communications. 2008 ; Vol. 365, No. 2. pp. 355-361.
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