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 T. Weintraub, David E. Bostwick, Marla Gearing, Allan I. Levey, Lih Shen Chin, Lian Li

Research output: Contribution to journalArticlepeer-review

345 Scopus citations

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

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'Oxidative damage of DJ-1 is linked to sporadic Parkinson and Alzheimer diseases'. Together they form a unique fingerprint.

Cite this