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Conjugates of Catecholamines with Cysteine and GSH in Parkinson's Disease: Possible Mechanisms of Formation Involving Reactive Oxygen Species
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Abstract: Oxidation of l ‐3,4‐dihydroxyphenylalanine ( l ‐DOPA) and dopamine (DA) to generate semiquinones/quinones, oxygen radicals, and other reactive oxygen species may play a role in neuronal cell death in Parkinson's disease (PD). In particular, semiquinones/quinones can form conjugates with thiol compounds such as GSH and cysteine. Exposure of l ‐DOPA, DA, and other catecholamines to a system generating O 2 •− radical led to O 2 •− ‐dependent depletion of added GSH (or cysteine), accompanied by the formation of thiol‐DA or ‐DOPA adducts as detected by HPLC. Superoxide could additionally cause destruction of these adducts. Iron or copper ions could also promote conjugate formation between GSH or cysteine and DA and l ‐DOPA, especially if H 2 O 2 was present. We applied HPLC to measure glutathionyl and cysteinyl conjugates of l ‐DOPA, DA, and 3,4‐dihydroxyphenylacetic acid (DOPAC) in postmortem brain samples from PD patients and normal control subjects. Conjugates were detected in most brain areas examined, but levels were highest in the substantia nigra and putamen. In most regions, adduct levels were lower in PD, but there were significant increases in cysteinyl adducts of l ‐DOPA, DA, and DOPAC in PD substantia nigra, suggesting that acceleration of l ‐DOPA/DA oxidation occurs in PD, although we cannot say if this is a primary feature of the disease or if it is related to therapy with l ‐DOPA. In vitro, conjugate formation could be inhibited by the dithiol dihydrolipoate but not by its oxidised form, lipoic acid.
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“Observation of cysteinyl adducts of dopamine in substantia nigra postmortem samples confirmed severe oxidation process occurring in PD brain. (Spencer et al. 1998).”
From Reactive Oxygen Species, Toxicity, Oxidative Stress, and Antioxidants: Chronic Diseases and Aging (2023) · cites this paper as Spencer et al. 1998
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- Halliwell B. and Gutteridge J. M. C. (1989) Free Radicals in Biol- ogy and Medicine, 2nd edit. Clarendon Press, Oxford.
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Metadata
- Authors
- Spencer, J. P. E., Jenner, P., Daniel, S. E., Lees, A. J., Marsden, D. C., & Halliwell, B.
- Affiliations
- University of London (GB)
- King's College London (GB)
- Parkinson's UK (GB)
- Corresponding author
- Spencer, Jeremy P. E.
- Venue
- Journal of Neurochemistry
- Publisher
- Wiley
- Published
- 1998-11
- Volume
- 71
- Issue
- 5
- Pages
- 2112-2122
- ISSN
- 0022-3042 (ISSN-L)
- 1471-4159
- OpenAlex
- W2165866163
- Cited by
- 373
- References
- 0
- Citations by year
- 2026: 4 · 2025: 7 · 2024: 6 · 2023: 9 · 2022: 8 · 2021: 7 · 2020: 8 · 2019: 10 · 2018: 2 · 2017: 11 · 2016: 10 · 2015: 14 · 2014: 15 · 2013: 12 · 2012: 19
- FWCI
- 12.67
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Neurochemistry (publishedVersion)
- PubMed (publishedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Topics
- Health Sciences › Medicine › Clinical Neurology › Parkinson's Disease Mechanisms and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Glutathione Transferases and Polymorphisms
- Keywords
- Parkinson's disease, catecholamines, L-DOPA, dopamine, glutathione conjugates, cysteine conjugates, reactive oxygen species, superoxide, semiquinone, quinones, oxidative stress, neuronal cell death, substantia nigra, putamen, alpha-lipoic acid, postmortem brain
- MeSH terms
- Aged, Aged, 80 and over, Chromatography, High Pressure Liquid, Copper, Cysteine, Dihydroxyphenylalanine, Dopamine, Glutathione, Humans, Iron, Parkinson Disease, Reference Values, Superoxides, 3,4-Dihydroxyphenylacetic Acid, 8,11,14-Eicosatrienoic Acid, Reactive Oxygen Species, Hypoxanthine, Xanthine
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