PMID- 12354300
OWN - NLM
STAT- MEDLINE
DCOM- 20021022
LR  - 20220410
IS  - 0022-3042 (Print)
IS  - 0022-3042 (Linking)
VI  - 82
IP  - 6
DP  - 2002 Sep
TI  - Proteomic identification of oxidatively modified proteins in Alzheimer's disease 
      brain. Part II: dihydropyrimidinase-related protein 2, alpha-enolase and heat 
      shock cognate 71.
PG  - 1524-32
AB  - Alzheimer's disease (AD) is a neurodegenerative disorder in which oxidative 
      stress has been implicated as an important event in the progression of the 
      pathology. In particular, it has been shown that protein modification by reactive 
      oxygen species (ROS) occurs to a greater extent in AD than in control brain, 
      suggesting a possible role for oxidation-related decrease in protein function in 
      the process of neurodegeneration. Oxidative damage to proteins, assessed by 
      measuring the protein carbonyl content, is involved in several events such as 
      loss in specific protein function, abnormal protein clearance, depletion of the 
      cellular redox-balance and interference with the cell cycle, and, ultimately, 
      neuronal death. The present investigation represents a further step in 
      understanding the relationship between oxidative modification of protein and 
      neuronal death in AD. Previously, we used our proteomics approach, which 
      successfully substitutes for labor-intensive immunochemical analysis, to detect 
      proteins and identified creatine kinase, glutamine synthase and ubiquitin 
      carboxy-terminal hydrolase L-1 as specifically oxidized proteins in AD brain. In 
      this report we again applied our proteomics approach to identify new targets of 
      protein oxidation in AD inferior parietal lobe (IPL). The dihydropyrimidinase 
      related protein 2 (DRP-2), which is involved in the axonal growth and guidance, 
      showed significantly increased level in protein carbonyls in AD brain, suggesting 
      a role for impaired mechanism of neural network formation in AD. Additionally, 
      the cytosolic enzyme alpha-enolase was identified as a target of protein 
      oxidation and is involved the glycolytic pathway in the pathological events of 
      AD. Finally, the heat shock cognate 71 (HSC-71) revealed increased, but not 
      significant, oxidation in AD brain. These results are discussed with reference to 
      potential involvement of these oxidatively modified proteins in neurodegeneration 
      in AD brain.
FAU - Castegna, Alessandra
AU  - Castegna A
AD  - Department of Chemistry, Center of Membrane Sciences, University of Kentucky, 
      Lexington, Kentucky 40506, USA.
FAU - Aksenov, Michael
AU  - Aksenov M
FAU - Thongboonkerd, Visith
AU  - Thongboonkerd V
FAU - Klein, Jon B
AU  - Klein JB
FAU - Pierce, William M
AU  - Pierce WM
FAU - Booze, Rosemarie
AU  - Booze R
FAU - Markesbery, William R
AU  - Markesbery WR
FAU - Butterfield, D Allan
AU  - Butterfield DA
LA  - eng
GR  - 5 P50 AG-05144/AG/NIA NIH HHS/United States
GR  - AG-05119/AG/NIA NIH HHS/United States
GR  - AG-10836/AG/NIA NIH HHS/United States
GR  - AG-12423/AG/NIA NIH HHS/United States
GR  - R01 HL66358-01/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - England
TA  - J Neurochem
JT  - Journal of neurochemistry
JID - 2985190R
RN  - 0 (HSC70 Heat-Shock Proteins)
RN  - 0 (HSP70 Heat-Shock Proteins)
RN  - 0 (HSPA8 protein, human)
RN  - 0 (Heat-Shock Proteins)
RN  - 0 (Intercellular Signaling Peptides and Proteins)
RN  - 0 (Nerve Tissue Proteins)
RN  - 0 (Proteins)
RN  - 0 (Proteome)
RN  - 0 (collapsin response mediator protein-2)
RN  - EC 4.2.1.11 (Phosphopyruvate Hydratase)
SB  - IM
MH  - Aged
MH  - Aged, 80 and over
MH  - Brain/*metabolism
MH  - Brain Chemistry
MH  - Electrophoresis, Gel, Two-Dimensional
MH  - Female
MH  - HSC70 Heat-Shock Proteins
MH  - *HSP70 Heat-Shock Proteins
MH  - Heat-Shock Proteins/analysis/*metabolism
MH  - Humans
MH  - Intercellular Signaling Peptides and Proteins
MH  - Male
MH  - Mass Spectrometry
MH  - Nerve Tissue Proteins
MH  - Oxidation-Reduction
MH  - Parietal Lobe/metabolism
MH  - Phosphopyruvate Hydratase/analysis/*metabolism
MH  - Proteins/analysis/*metabolism
MH  - Proteome
EDAT- 2002/10/02 04:00
MHDA- 2002/10/31 04:00
CRDT- 2002/10/02 04:00
PHST- 2002/10/02 04:00 [pubmed]
PHST- 2002/10/31 04:00 [medline]
PHST- 2002/10/02 04:00 [entrez]
AID - 1103 [pii]
AID - 10.1046/j.1471-4159.2002.01103.x [doi]
PST - ppublish
SO  - J Neurochem. 2002 Sep;82(6):1524-32. doi: 10.1046/j.1471-4159.2002.01103.x.