The DOI matches its Crossref record; 52 of the 55 references it cites were found in a registry or an index.
Increase of oxidative stress by a novel PINK1 mutation, P209A
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.
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Mutated PINK1 is characterized by severe oxidative stress-induced cell death.
“Mutated PINK1 is characterized by severe oxidative stress-induced cell death (Chien et al. 2013; Dias et al. 2013).”
From Reactive Oxygen Species, Toxicity, Oxidative Stress, and Antioxidants: Chronic Diseases and Aging (2023) · cites this paper as Chien et al. 2013
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Metadata
- Authors
- Chien, W.-L., Lee, T.-R., Hung, S.-Y., Kang, K.-H., Wu, R.-M., Lee, M.-J., & Fu, W.-M.
- Affiliations
- National Taiwan University (TW)
- Corresponding author
- Lee, Tzeng-Ruei
- Lee, Ming-Jen
- Fu, Wen-Mei
- Venue
- Free Radical Biology and Medicine
- Publisher
- Elsevier BV
- Published
- 2013-05
- Volume
- 58
- Pages
- 160-169
- ISSN
- 0891-5849 (ISSN-L)
- OpenAlex
- W2072995415
- Cited by
- 19
- References
- 55
- Citations by year
- 2025: 1 · 2024: 1 · 2023: 2 · 2020: 3 · 2019: 2 · 2018: 4 · 2016: 3 · 2015: 2 · 2013: 1
- FWCI
- 0.63
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Free Radical Biology and Medicine (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Science Council and National Taiwan University (98R0066-53)
- Topics
- Health Sciences › Medicine › Clinical Neurology › Parkinson's Disease Mechanisms and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nuclear Receptors and Signaling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Coenzyme Q10 studies and effects
- Keywords
- PINK1, Parkinson's disease, oxidative stress, heme oxygenase-1, manganese superoxide dismutase, MPP+, hydrogen peroxide, caspase-3, Akt signaling, ERK signaling, neurodegeneration, SH-SY5Y cells
- MeSH terms
- Superoxide Dismutase 2, PTEN-Induced Putative Kinase, Cell Line, Female, Heterozygote, Humans, Levodopa, Male, Mutation, Parkinson Disease, Phosphorylation, Protein Kinases, Superoxide Dismutase, Age of Onset, Oxidative Stress, Genetic Predisposition to Disease, Heme Oxygenase-1
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