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

Joungil Choi, M. Cameron Sullards, James A. Olzmann, Howard D. Rees, Susan E Weintraub, David E. Bostwick, Marla Gearing, Allan I. Levey, Lih Shen Chin, Lian Li

Research output: Contribution to journalArticle

331 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)10816-10824
Number of pages9
JournalJournal of Biological Chemistry
Volume281
Issue number16
DOIs
StatePublished - Apr 21 2006

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Parkinson Disease
Alzheimer Disease
Protein Isoforms
Methionine
Mass Spectrometry
Electrophoresis, Gel, Two-Dimensional
Brain
Frontal Lobe
Oxidation
Mass spectrometry
Neurodegenerative Diseases
Cysteine
Western Blotting
Neurodegenerative diseases
Carbonylation
Mutation
Electrophoresis
Dimers
Proteins
Monomers

ASJC Scopus subject areas

  • Biochemistry

Cite this

Choi, J., Sullards, M. C., Olzmann, J. A., Rees, H. D., Weintraub, S. E., Bostwick, D. E., ... Li, L. (2006). Oxidative damage of DJ-1 is linked to sporadic Parkinson and Alzheimer diseases. Journal of Biological Chemistry, 281(16), 10816-10824. https://doi.org/10.1074/jbc.M509079200

Oxidative damage of DJ-1 is linked to sporadic Parkinson and Alzheimer diseases. / Choi, Joungil; Sullards, M. Cameron; Olzmann, James A.; Rees, Howard D.; Weintraub, Susan E; Bostwick, David E.; Gearing, Marla; Levey, Allan I.; Chin, Lih Shen; Li, Lian.

In: Journal of Biological Chemistry, Vol. 281, No. 16, 21.04.2006, p. 10816-10824.

Research output: Contribution to journalArticle

Choi, J, Sullards, MC, Olzmann, JA, Rees, HD, Weintraub, SE, Bostwick, DE, Gearing, M, Levey, AI, Chin, LS & Li, L 2006, 'Oxidative damage of DJ-1 is linked to sporadic Parkinson and Alzheimer diseases', Journal of Biological Chemistry, vol. 281, no. 16, pp. 10816-10824. https://doi.org/10.1074/jbc.M509079200
Choi, Joungil ; Sullards, M. Cameron ; Olzmann, James A. ; Rees, Howard D. ; Weintraub, Susan E ; Bostwick, David E. ; Gearing, Marla ; Levey, Allan I. ; Chin, Lih Shen ; Li, Lian. / Oxidative damage of DJ-1 is linked to sporadic Parkinson and Alzheimer diseases. In: Journal of Biological Chemistry. 2006 ; Vol. 281, No. 16. pp. 10816-10824.
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