The DOI matches its Crossref record; 75 of the 75 references it cites were found in a registry or an index.
The Parkinsonism-inducing Drug 1-Methyl-4-phenylpyridinium Triggers Intracellular Dopamine Oxidation
Open accessAbstract
Uptake of the Parkinsonism-inducing toxin, 1-methyl-4-phenylpyridinium (MPP(+)), into dopaminergic terminals is thought to block Complex I activity leading to ATP loss and overproduction of reactive oxygen species (ROS). The present study indicates that MPP(+)-induced ROS formation is not mitochondrial in origin but results from intracellular dopamine (DA) oxidation. Although a mean lethal dose of MPP(+) led to ROS production in identified dopaminergic neurons, toxic doses of the Complex I inhibitor rotenone did not. Concurrent with ROS formation, MPP(+) redistributed vesicular DA to the cytoplasm prior to its extrusion from the cell by reverse transport via the DA transporter. MPP(+)-induced DA redistribution was also associated with cell death. Depleting cells of newly synthesized and/or stored DA significantly attenuated both superoxide production and cell death, whereas enhancing intracellular DA content exacerbated dopaminergic sensitivity to MPP(+). Lastly, depleting cells of DA in the presence of succinate completely abolished MPP(+)-induced cell death. Thus, MPP(+) neurotoxicity is a multi-component process involving both mitochondrial dysfunction and ROS generated by vesicular DA displacement. These results suggest that in the presence of a Complex I defect, misregulation of DA storage could lead to the loss of nigrostriatal neurons in Parkinson's disease.
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Cites
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Cited by
Oxidative stress in Parkinson's disease
Jenner, P. (2003) · Annals of Neurology · doi:10.1002/ana.10483 · Cited by 2,053
Mechanism of Oxidative Stress in Neurodegeneration
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DJ‐1 has a role in antioxidative stress to prevent cell death
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Oxidative stress and nitration in neurodegeneration: Cause, effect, or association?
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Metadata
- Authors
- Lotharius, J., & O'Malley, K. L.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2000-12
- Volume
- 275
- Issue
- 49
- Pages
- 38581-38588
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2052122668
- Cited by
- 306
- References
- 75
- FWCI
- 11.52
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- Lotharius, J., & O'Malley, K. L. (2000). The Parkinsonism-inducing Drug 1-Methyl-4-phenylpyridinium Triggers Intracellular Dopamine Oxidation. Journal of Biological Chemistry. https://doi.org/10.1074/jbc.m005385200
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Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
