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 language | English (US) |
|---|---|
| Pages (from-to) | 1155-1162 |
| Number of pages | 8 |
| Journal | Free Radical Biology and Medicine |
| Volume | 36 |
| Issue number | 9 |
| DOIs | |
| State | Published - May 1 2004 |
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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 journal › Article
}
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 -