Cargando…

Kinetic Modeling of pH-Dependent Oxidation of Dopamine by Iron and Its Relevance to Parkinson's Disease

Parkinson's disease is the second most common neurodegenerative disease. While age is the most significant risk factor, the exact cause of this disease and the most effective approaches to mitigation remain unclear. It has long been proposed that dopamine may play a role in the pathology of Par...

Descripción completa

Detalles Bibliográficos
Autores principales: Sun, Yingying, Pham, A. Ninh, Hare, Dominic J., Waite, T. David
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6275323/
https://www.ncbi.nlm.nih.gov/pubmed/30534046
http://dx.doi.org/10.3389/fnins.2018.00859
_version_ 1783377802636034048
author Sun, Yingying
Pham, A. Ninh
Hare, Dominic J.
Waite, T. David
author_facet Sun, Yingying
Pham, A. Ninh
Hare, Dominic J.
Waite, T. David
author_sort Sun, Yingying
collection PubMed
description Parkinson's disease is the second most common neurodegenerative disease. While age is the most significant risk factor, the exact cause of this disease and the most effective approaches to mitigation remain unclear. It has long been proposed that dopamine may play a role in the pathology of Parkinson's disease in view of its ability to generate both protein-modifying quinones such as aminochrome and reactive oxygen species, especially in the presence of pathological iron accumulation in the primary site of neuron loss. Given the clinically measured acidosis of post-mortem Parkinson's disease brain tissue, the interaction between dopamine and iron was investigated over a pH range of 7.4 to 6.5 with emphasis on the accumulation of toxic quinones and generation of reactive oxygen species. Our results show that the presence of iron accelerates the formation of aminochrome with ferrous iron (Fe[II]) being more efficient in this regard than ferric iron (Fe[III]). Our results further suggest that a reduced aminochrome rearrangement rate coupled with an enhanced turnover rate of Fe[II] as a result of brain tissue acidosis could result in aminochrome accumulation within cells. Additionally, under these conditions, the enhanced redox cycling of iron in the presence of dopamine aggravates oxidative stress as a result of the production of damaging reactive species, including hydroxyl radicals.
format Online
Article
Text
id pubmed-6275323
institution National Center for Biotechnology Information
language English
publishDate 2018
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-62753232018-12-10 Kinetic Modeling of pH-Dependent Oxidation of Dopamine by Iron and Its Relevance to Parkinson's Disease Sun, Yingying Pham, A. Ninh Hare, Dominic J. Waite, T. David Front Neurosci Neuroscience Parkinson's disease is the second most common neurodegenerative disease. While age is the most significant risk factor, the exact cause of this disease and the most effective approaches to mitigation remain unclear. It has long been proposed that dopamine may play a role in the pathology of Parkinson's disease in view of its ability to generate both protein-modifying quinones such as aminochrome and reactive oxygen species, especially in the presence of pathological iron accumulation in the primary site of neuron loss. Given the clinically measured acidosis of post-mortem Parkinson's disease brain tissue, the interaction between dopamine and iron was investigated over a pH range of 7.4 to 6.5 with emphasis on the accumulation of toxic quinones and generation of reactive oxygen species. Our results show that the presence of iron accelerates the formation of aminochrome with ferrous iron (Fe[II]) being more efficient in this regard than ferric iron (Fe[III]). Our results further suggest that a reduced aminochrome rearrangement rate coupled with an enhanced turnover rate of Fe[II] as a result of brain tissue acidosis could result in aminochrome accumulation within cells. Additionally, under these conditions, the enhanced redox cycling of iron in the presence of dopamine aggravates oxidative stress as a result of the production of damaging reactive species, including hydroxyl radicals. Frontiers Media S.A. 2018-11-26 /pmc/articles/PMC6275323/ /pubmed/30534046 http://dx.doi.org/10.3389/fnins.2018.00859 Text en Copyright © 2018 Sun, Pham, Hare and Waite. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Neuroscience
Sun, Yingying
Pham, A. Ninh
Hare, Dominic J.
Waite, T. David
Kinetic Modeling of pH-Dependent Oxidation of Dopamine by Iron and Its Relevance to Parkinson's Disease
title Kinetic Modeling of pH-Dependent Oxidation of Dopamine by Iron and Its Relevance to Parkinson's Disease
title_full Kinetic Modeling of pH-Dependent Oxidation of Dopamine by Iron and Its Relevance to Parkinson's Disease
title_fullStr Kinetic Modeling of pH-Dependent Oxidation of Dopamine by Iron and Its Relevance to Parkinson's Disease
title_full_unstemmed Kinetic Modeling of pH-Dependent Oxidation of Dopamine by Iron and Its Relevance to Parkinson's Disease
title_short Kinetic Modeling of pH-Dependent Oxidation of Dopamine by Iron and Its Relevance to Parkinson's Disease
title_sort kinetic modeling of ph-dependent oxidation of dopamine by iron and its relevance to parkinson's disease
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6275323/
https://www.ncbi.nlm.nih.gov/pubmed/30534046
http://dx.doi.org/10.3389/fnins.2018.00859
work_keys_str_mv AT sunyingying kineticmodelingofphdependentoxidationofdopaminebyironanditsrelevancetoparkinsonsdisease
AT phamaninh kineticmodelingofphdependentoxidationofdopaminebyironanditsrelevancetoparkinsonsdisease
AT haredominicj kineticmodelingofphdependentoxidationofdopaminebyironanditsrelevancetoparkinsonsdisease
AT waitetdavid kineticmodelingofphdependentoxidationofdopaminebyironanditsrelevancetoparkinsonsdisease