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

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

doi:10.1016/j.bbrc.2007.10.194

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

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

Biochemistry & Molecular Biology

Research output: Contribution to journal › Article › peer-review

117 Scopus citations

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 language	English (US)
Pages (from-to)	355-361
Number of pages	7
Journal	Biochemical and Biophysical Research Communications
Volume	365
Issue number	2
DOIs	https://doi.org/10.1016/j.bbrc.2007.10.194
State	Published - Jan 11 2008

Keywords

Aging
BiP
Carbonylation
Chaperone modification
Oxidative stress
PDI
Protein folding

ASJC Scopus subject areas

Biophysics
Biochemistry
Molecular Biology
Cell Biology

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10.1016/j.bbrc.2007.10.194

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title = "Decreased enzyme activities of chaperones PDI and BiP in aged mouse livers",

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.",

keywords = "Aging, BiP, Carbonylation, Chaperone modification, Oxidative stress, PDI, Protein folding",

author = "Nuss, {Jonathan E.} and Choksi, {Kashyap B.} and DeFord, {James H.} and John Papaconstantinou",

note = "Funding Information: This publication was supported by U.S.P.H.S. Grant 1P01 AG021830 awarded by the National Institute on Aging, and the National Institute on Aging 1 P30 AG024832-03 Claude D. Pepper Older Americans Independence Center grant, and by the UTMB Sealy Center on Aging. J.E.N. thank the Kempner Foundation and the National Institutes of Environmental Health Sciences, Training Grant (T32-07254) for their fellowship support.",

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doi = "10.1016/j.bbrc.2007.10.194",

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AU - DeFord, James H.

AU - Papaconstantinou, John

N1 - Funding Information: This publication was supported by U.S.P.H.S. Grant 1P01 AG021830 awarded by the National Institute on Aging, and the National Institute on Aging 1 P30 AG024832-03 Claude D. Pepper Older Americans Independence Center grant, and by the UTMB Sealy Center on Aging. J.E.N. thank the Kempner Foundation and the National Institutes of Environmental Health Sciences, Training Grant (T32-07254) for their fellowship support.

PY - 2008/1/11

Y1 - 2008/1/11

N2 - 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.

AB - 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.

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

Abstract

Keywords

ASJC Scopus subject areas

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