Display Settings:

Format

Send to:

Choose Destination
See comment in PubMed Commons below
Free Radic Biol Med. 2013 May;58:160-9. doi: 10.1016/j.freeradbiomed.2012.12.008. Epub 2012 Dec 20.

Increase of oxidative stress by a novel PINK1 mutation, P209A.

Author information

  • 1Pharmacological Institute, College of Medicine, National Taiwan University, Taipei, Taiwan.

Abstract

Mutation in the human PTEN-induced protein kinase 1 (PINK1) gene is responsible for the second most common form of recessive Parkinson disease (PD). We have identified a single heterozygous PINK1 mutation, P209A, from a cohort of 68 patients with early onset PD. From age 31, this patient developed an asymmetric bradykinesia with rigidity that was L-DOPA responsive. An [(18)F]-fluorodopa PET scan showed reduced DOPA uptake in the bilateral basal ganglia. The H2O2-induced cell death, ROS production, and caspase-3 activation in SH-SY5Y cells were enhanced by the transfection of the PINK1 P209A mutant. The heme oxygenase-1 (HO-1) induction in response to H2O2 and MPP(+) treatment was impaired by the overexpression of the PINK1 P209A mutant. In addition, SOD2 induction after TNFα treatment was also inhibited by the PINK1 P209A mutation. Akt and ERK are involved in HO-1 induction after oxidative stress. The phosphorylation of Akt and ERK after exposure to H2O2 or MPP(+) was also inhibited in PINK1 P209A mutant cells compared with empty-vector-transfected cells. These results indicate a novel pathway by which the P209A defect in the PINK1 kinase domain inhibits oxidative stress-induced HO-1 and SOD2 induction, which may accelerate the neurodegeneration in PD with PINK1 defect.

Crown Copyright © 2012. Published by Elsevier Inc. All rights reserved.

PMID:
23261939
[PubMed - indexed for MEDLINE]
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Icon for Elsevier Science
    Loading ...
    Write to the Help Desk