Proteomic identification of specific oxidized proteins in ApoE-knockout mice: Relevance to Alzheimer's disease

Joungil Choi, Michael J. Forster, Shelley R. McDonald, Susan E Weintraub, Christopher A. Carroll, Robert W. Gracy

Research output: Contribution to journalArticle

91 Citations (Scopus)

Abstract

We have examined oxidized proteins in the brain regions of wild-type (WT) and ApoE-knockout (KO) animals. Total protein oxidation in the hippocampus of young-KO (6 month) animals was approximately 2-fold greater than that of young-WT (6 month) animals and was similar to that of old-WT (18 month) and old-KO (18 month) animals. In the cortex of the same animals, the levels of total protein oxidation in all four groups were not significantly different. Two-dimensional electrophoresis (2-DE) coupled with immunostaining for protein carbonylation revealed six specific oxidation-sensitive proteins, the oxidation levels of which were increased in young-KO, old-WT, and old-KO mice compared with young-WT mice. These six oxidation-sensitive proteins were identified by mass spectrometry as glial fibrillary acidic protein, creatine kinase BB, disulfide isomerase, chaperonin subunit 5, dihydropyrimidase-related protein 2, and mortalin. These results indicate that the ApoE gene product offers protection against age-associated oxidative damage in the brain. Moreover, two of these proteins, creatine kinase and dihydropyrimidase-related protein 2, have recently been found to be oxidized in the brains of human subjects with Alzheimer's disease [Aksenov et al. J. Neurochem. 74: 2520-2527; 2000; Castegna et al. J. Neurochem. 82: 1524-1532; 2002]. These data suggest that the ApoE-knockout mouse serves as an appropriate model for studying pathogenic oxidative mechanisms influencing risk and progression of Alzheimer's disease.

Original languageEnglish (US)
Pages (from-to)1155-1162
Number of pages8
JournalFree Radical Biology and Medicine
Volume36
Issue number9
DOIs
StatePublished - May 1 2004

Fingerprint

Apolipoproteins E
Knockout Mice
Proteomics
Alzheimer Disease
Animals
Proteins
Oxidation
Creatine Kinase
Brain
Protein Kinases
Protein Carbonylation
Chaperonins
Protein Disulfide-Isomerases
BB Form Creatine Kinase
Glial Fibrillary Acidic Protein
Carbonylation
Electrophoresis
Hippocampus
Mass Spectrometry
Mass spectrometry

Keywords

  • Alzheimer's disease
  • ApoE-knockout mice
  • Chaperonin subunit 5
  • Creatine kinase
  • Dihydropyrimidase-like 2
  • Disulfide isomerase
  • Free radicals
  • Glial fibrillary acidic protein
  • Mass spectrometry
  • Mortalin
  • Protein oxidation
  • Two-dimensional gel electrophoresis

ASJC Scopus subject areas

  • Medicine(all)
  • Toxicology
  • Clinical Biochemistry

Cite this

Proteomic identification of specific oxidized proteins in ApoE-knockout mice : Relevance to Alzheimer's disease. / Choi, Joungil; Forster, Michael J.; McDonald, Shelley R.; Weintraub, Susan E; Carroll, Christopher A.; Gracy, Robert W.

In: Free Radical Biology and Medicine, Vol. 36, No. 9, 01.05.2004, p. 1155-1162.

Research output: Contribution to journalArticle

Choi, Joungil ; Forster, Michael J. ; McDonald, Shelley R. ; Weintraub, Susan E ; Carroll, Christopher A. ; Gracy, Robert W. / Proteomic identification of specific oxidized proteins in ApoE-knockout mice : Relevance to Alzheimer's disease. In: Free Radical Biology and Medicine. 2004 ; Vol. 36, No. 9. pp. 1155-1162.
@article{47bada3b24984af6bc34db76c230bb83,
title = "Proteomic identification of specific oxidized proteins in ApoE-knockout mice: Relevance to Alzheimer's disease",
abstract = "We have examined oxidized proteins in the brain regions of wild-type (WT) and ApoE-knockout (KO) animals. Total protein oxidation in the hippocampus of young-KO (6 month) animals was approximately 2-fold greater than that of young-WT (6 month) animals and was similar to that of old-WT (18 month) and old-KO (18 month) animals. In the cortex of the same animals, the levels of total protein oxidation in all four groups were not significantly different. Two-dimensional electrophoresis (2-DE) coupled with immunostaining for protein carbonylation revealed six specific oxidation-sensitive proteins, the oxidation levels of which were increased in young-KO, old-WT, and old-KO mice compared with young-WT mice. These six oxidation-sensitive proteins were identified by mass spectrometry as glial fibrillary acidic protein, creatine kinase BB, disulfide isomerase, chaperonin subunit 5, dihydropyrimidase-related protein 2, and mortalin. These results indicate that the ApoE gene product offers protection against age-associated oxidative damage in the brain. Moreover, two of these proteins, creatine kinase and dihydropyrimidase-related protein 2, have recently been found to be oxidized in the brains of human subjects with Alzheimer's disease [Aksenov et al. J. Neurochem. 74: 2520-2527; 2000; Castegna et al. J. Neurochem. 82: 1524-1532; 2002]. These data suggest that the ApoE-knockout mouse serves as an appropriate model for studying pathogenic oxidative mechanisms influencing risk and progression of Alzheimer's disease.",
keywords = "Alzheimer's disease, ApoE-knockout mice, Chaperonin subunit 5, Creatine kinase, Dihydropyrimidase-like 2, Disulfide isomerase, Free radicals, Glial fibrillary acidic protein, Mass spectrometry, Mortalin, Protein oxidation, Two-dimensional gel electrophoresis",
author = "Joungil Choi and Forster, {Michael J.} and McDonald, {Shelley R.} and Weintraub, {Susan E} and Carroll, {Christopher A.} and Gracy, {Robert W.}",
year = "2004",
month = "5",
day = "1",
doi = "10.1016/j.freeradbiomed.2004.02.002",
language = "English (US)",
volume = "36",
pages = "1155--1162",
journal = "Free Radical Biology and Medicine",
issn = "0891-5849",
publisher = "Elsevier Inc.",
number = "9",

}

TY - JOUR

T1 - Proteomic identification of specific oxidized proteins in ApoE-knockout mice

T2 - Relevance to Alzheimer's disease

AU - Choi, Joungil

AU - Forster, Michael J.

AU - McDonald, Shelley R.

AU - Weintraub, Susan E

AU - Carroll, Christopher A.

AU - Gracy, Robert W.

PY - 2004/5/1

Y1 - 2004/5/1

N2 - We have examined oxidized proteins in the brain regions of wild-type (WT) and ApoE-knockout (KO) animals. Total protein oxidation in the hippocampus of young-KO (6 month) animals was approximately 2-fold greater than that of young-WT (6 month) animals and was similar to that of old-WT (18 month) and old-KO (18 month) animals. In the cortex of the same animals, the levels of total protein oxidation in all four groups were not significantly different. Two-dimensional electrophoresis (2-DE) coupled with immunostaining for protein carbonylation revealed six specific oxidation-sensitive proteins, the oxidation levels of which were increased in young-KO, old-WT, and old-KO mice compared with young-WT mice. These six oxidation-sensitive proteins were identified by mass spectrometry as glial fibrillary acidic protein, creatine kinase BB, disulfide isomerase, chaperonin subunit 5, dihydropyrimidase-related protein 2, and mortalin. These results indicate that the ApoE gene product offers protection against age-associated oxidative damage in the brain. Moreover, two of these proteins, creatine kinase and dihydropyrimidase-related protein 2, have recently been found to be oxidized in the brains of human subjects with Alzheimer's disease [Aksenov et al. J. Neurochem. 74: 2520-2527; 2000; Castegna et al. J. Neurochem. 82: 1524-1532; 2002]. These data suggest that the ApoE-knockout mouse serves as an appropriate model for studying pathogenic oxidative mechanisms influencing risk and progression of Alzheimer's disease.

AB - We have examined oxidized proteins in the brain regions of wild-type (WT) and ApoE-knockout (KO) animals. Total protein oxidation in the hippocampus of young-KO (6 month) animals was approximately 2-fold greater than that of young-WT (6 month) animals and was similar to that of old-WT (18 month) and old-KO (18 month) animals. In the cortex of the same animals, the levels of total protein oxidation in all four groups were not significantly different. Two-dimensional electrophoresis (2-DE) coupled with immunostaining for protein carbonylation revealed six specific oxidation-sensitive proteins, the oxidation levels of which were increased in young-KO, old-WT, and old-KO mice compared with young-WT mice. These six oxidation-sensitive proteins were identified by mass spectrometry as glial fibrillary acidic protein, creatine kinase BB, disulfide isomerase, chaperonin subunit 5, dihydropyrimidase-related protein 2, and mortalin. These results indicate that the ApoE gene product offers protection against age-associated oxidative damage in the brain. Moreover, two of these proteins, creatine kinase and dihydropyrimidase-related protein 2, have recently been found to be oxidized in the brains of human subjects with Alzheimer's disease [Aksenov et al. J. Neurochem. 74: 2520-2527; 2000; Castegna et al. J. Neurochem. 82: 1524-1532; 2002]. These data suggest that the ApoE-knockout mouse serves as an appropriate model for studying pathogenic oxidative mechanisms influencing risk and progression of Alzheimer's disease.

KW - Alzheimer's disease

KW - ApoE-knockout mice

KW - Chaperonin subunit 5

KW - Creatine kinase

KW - Dihydropyrimidase-like 2

KW - Disulfide isomerase

KW - Free radicals

KW - Glial fibrillary acidic protein

KW - Mass spectrometry

KW - Mortalin

KW - Protein oxidation

KW - Two-dimensional gel electrophoresis

UR - http://www.scopus.com/inward/record.url?scp=1842634504&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=1842634504&partnerID=8YFLogxK

U2 - 10.1016/j.freeradbiomed.2004.02.002

DO - 10.1016/j.freeradbiomed.2004.02.002

M3 - Article

C2 - 15082069

AN - SCOPUS:1842634504

VL - 36

SP - 1155

EP - 1162

JO - Free Radical Biology and Medicine

JF - Free Radical Biology and Medicine

SN - 0891-5849

IS - 9

ER -