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

被引:86
作者
Choi, J
Forster, MJ
McDonald, SR
Weintraub, ST
Carroll, CA
Gracy, RW
机构
[1] Univ N Texas, Ctr Hlth Sci, Dept Mol Biol & Immunol, Mol Aging Unit, Ft Worth, TX 76107 USA
[2] Univ N Texas, Ctr Hlth Sci, Dept Pharmacol & Neurosci, Ft Worth, TX 76107 USA
[3] Univ Texas, Hlth Sci Ctr, Dept Biochem, San Antonio, TX 78229 USA
关键词
protein oxidation; two-dimensional gel electrophoresis; ApoE-knockout mice; Alzheimer's disease; glial fibrillary acidic protein; creatine kinase; disulfide isomerase; chaperonin subunit 5; dihydropyrimidase-like; 2; mortalin; mass spectrometry; free radicals;
D O I
10.1016/j.freeradbiomed.2004.02.002
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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. (C) 2004 Elsevier Inc. All rights reserved.
引用
收藏
页码:1155 / 1162
页数:8
相关论文
共 39 条
[1]   Oxidative modification of creatine kinase BB in Alzheimer's disease brain [J].
Aksenov, M ;
Aksenova, M ;
Butterfield, DA ;
Markesbery, WR .
JOURNAL OF NEUROCHEMISTRY, 2000, 74 (06) :2520-2527
[2]   Protein oxidation in aging, disease, and oxidative stress [J].
Berlett, BS ;
Stadtman, ER .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1997, 272 (33) :20313-20316
[3]   Mutations in GFAP, encoding glial fibrillary acidic protein, are associated with Alexander disease [J].
Brenner, M ;
Johnson, AB ;
Boespflug-Tanguy, O ;
Rodriguez, D ;
Goldman, JE ;
Messing, A .
NATURE GENETICS, 2001, 27 (01) :117-120
[4]  
Buttini M, 1999, J NEUROSCI, V19, P4867
[5]   Proteomic identification of oxidatively modified proteins in Alzheimer's disease brain.: Part II:: dihydropyrimidinase-related protein 2, α-enolase and heat shock cognate 71 [J].
Castegna, A ;
Aksenov, M ;
Thongboonkerd, V ;
Klein, JB ;
Pierce, WM ;
Booze, R ;
Markesbery, WR ;
Butterfield, DA .
JOURNAL OF NEUROCHEMISTRY, 2002, 82 (06) :1524-1532
[6]  
CASTEGNA A, 2000, FREE RADIC BIOL MED, V33, P562
[7]   Identification of oxidized plasma proteins in Alzheimer's disease [J].
Choi, JG ;
Malakowsky, CA ;
Talent, JM ;
Conrad, CC ;
Gracy, RW .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2002, 293 (05) :1566-1570
[8]   Flavones from Scutellaria baicalensis Georgi attenuate apoptosis and protein oxidation in neuronal cell lines [J].
Choi, JG ;
Conrad, CC ;
Malakowsky, CA ;
Talent, JM ;
Yuan, CS ;
Gracy, RW .
BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS, 2002, 1571 (03) :201-210
[9]   APOE and the regulation of microglial nitric oxide production:: a link between genetic risk and oxidative stress [J].
Colton, CA ;
Brown, CM ;
Cook, D ;
Needham, LK ;
Xu, Q ;
Czapiga, M ;
Saunders, AM ;
Schmechel, DE ;
Rasheed, K ;
Vitek, MP .
NEUROBIOLOGY OF AGING, 2002, 23 (05) :777-785
[10]   Oxidized proteins in Alzheimer's plasma [J].
Conrad, CC ;
Marshall, PL ;
Talent, JM ;
Malakowsky, CA ;
Choi, J ;
Gracy, RW .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2000, 275 (02) :678-681