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PMID: 16517609 Published · ppublish English Journal Article Research Support, N.I.H., Extramural

Oxidative damage of DJ-1 is linked to sporadic Parkinson and Alzheimer diseases.

The Journal of biological chemistry ·Vol. 281 ·No. 16 ·2006-04-21 ·Pages 10816-24

Choi J, Sullards MC, Olzmann JA, Rees HD, Weintraub ST, Bostwick DE, Gearing M, Levey AI, Chin LS, Li L

Abstract

Mutations in DJ-1 cause an autosomal recessive, early onset familial form of Parkinson disease (PD). However, little is presently known about the role of DJ-1 in the more common sporadic form of PD and in other age-related neurodegenerative diseases, such as Alzheimer disease (AD). Here we report that DJ-1 is oxidatively damaged in the brains of patients with idiopathic PD and AD. By using a combination of two-dimensional gel electrophoresis and mass spectrometry, we have identified 10 different DJ-1 isoforms, of which the acidic isoforms (pI 5.5 and 5.7) of DJ-1 monomer and the basic isoforms (pI 8.0 and 8.4) of SDS-resistant DJ-1 dimer are selectively accumulated in PD and AD frontal cortex tissues compared with age-matched controls. Quantitative Western blot analysis shows that the total level of DJ-1 protein is significantly increased in PD and AD brains. Mass spectrometry analyses reveal that DJ-1 is not only susceptible to cysteine oxidation but also to previously unsuspected methionine oxidation. Furthermore, we show that DJ-1 protein is irreversibly oxidized by carbonylation as well as by methionine oxidation to methionine sulfone in PD and AD. Our study provides new insights into the oxidative modifications of DJ-1 and indicates association of oxidative damage to DJ-1 with sporadic PD and AD.

MeSH Terms
2,4-Dinitrophenol/chemistry Aged Aged, 80 and over Alzheimer Disease/pathology Amino Acid Sequence Blotting, Western Brain/metabolism,pathology Carbon/chemistry Cerebral Cortex/pathology Dimerization Electrophoresis, Gel, Two-Dimensional Female Humans Intracellular Signaling Peptides and Proteins Isoelectric Point Lipid Peroxidation Lipids/chemistry Male Mass Spectrometry Methionine/chemistry Middle Aged Molecular Sequence Data Neurodegenerative Diseases Oncogene Proteins/metabolism,physiology Oxidative Stress Oxygen/chemistry,metabolism Parkinson Disease/metabolism,pathology Peptides/chemistry Protein Deglycase DJ-1 Protein Isoforms Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization Time Factors
Chemicals
Intracellular Signaling Peptides and Proteins Lipids Oncogene Proteins Peptides Protein Isoforms Carbon Methionine PARK7 protein, human Protein Deglycase DJ-1 2,4-Dinitrophenol Oxygen
Authors & Affiliations
10 authors, click to expand affiliations / ORCID
Choi Joungil
Department of Pharmacology, Center for Neurodegenerative Disease, Emory University School of Medicine, Atlanta, Georgia 30322, USA.
Sullards M Cameron
Olzmann James A
Rees Howard D
Weintraub Susan T
Bostwick David E
Gearing Marla
Levey Allan I
Chin Lih-Shen
Li Lian
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Article Info
Journal
The Journal of biological chemistry
Abbr.
J Biol Chem
ISSN
0021-9258
DOI
10.1074/jbc.M509079200
Published
2006-04-21
Epub
2006-00-03
Pages
10816-24
Language
English
Region
United States
NLM ID
2985121R
PMCID
PMC1850953
Subset
IM
Grants
NINDS NIH HHS · F31 NS054597-02 · United States
NINDS NIH HHS · R01 NS050650 · United States
NIA NIH HHS · AG021489 · United States
NCI NIH HHS · CA54174 · United States
NINDS NIH HHS · NS050650 · United States
NINDS NIH HHS · F31 NS054597-01 · United States
NIA NIH HHS · R01 AG021489 · United States
NINDS NIH HHS · NS047199 · United States
NIA NIH HHS · AG025688 · United States
NIA NIH HHS · P50 AG025688 · United States
NINDS NIH HHS · F31 NS054597 · United States
NINDS NIH HHS · R01 NS047575 · United States
NCI NIH HHS · P30 CA054174 · United States
NINDS NIH HHS · NS047575 · United States
NINDS NIH HHS · R01 NS047199 · United States
External Links
PubMed source DOI: 10.1074/jbc.M509079200 PMC Full Text View journal details
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