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Peroxynitrite induced formation of the neurotoxins 5-S-cysteinyl-dopamine and DHBT-1: implications for Parkinson's disease and protection by polyphenols

Vauzour, D., Ravaioli, G., Vafeiadou, K., Rodriguez-Mateos, A., Angeloni, C. and Spencer, J. P. E. ORCID: https://orcid.org/0000-0003-2931-7274 (2008) Peroxynitrite induced formation of the neurotoxins 5-S-cysteinyl-dopamine and DHBT-1: implications for Parkinson's disease and protection by polyphenols. Archives of Biochemistry and Biophysics, 476 (2). pp. 145-151. ISSN 0003-9861

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To link to this item DOI: 10.1016/j.abb.2008.03.011

Abstract/Summary

Mechanisms of nigral cell injury in Parkinson's disease remain unclear, although a combination of increased oxidative stress, the formation of catecholamine-quinones and the subsequent formation of neurotoxic cysteinyl-catecholamine conjugates may contribute. In the present study, peroxynitrite was observed to generate both 2-S- and 5-S-cysteinyl-dopamine and a dihydrobenzothiazine species, DHBT-1, following the reaction of dopamine with L-cysteine. The formation of 5-S-cysteinyl-dopamine and DHBT-1 in the presence of peroxynitrite induced significant neuronal injury. Pre-treatment of cortical neurons with pelargonidin, quercetin, hesperetin, caffeic acid, the 4'-O-Me derivatives of catechin and epicatechin (0.1-3.0 mu M) resulted in concentration dependant protection against 5-S-cysteinyl-dopamine-induced neurotoxicity. These data suggest that polyphenols may protect against neuronal injury induced by endogenous neurotoxins relevant to the aetiology of the Parkinson disease. (C) 2008 Elsevier Inc. All rights reserved.

Item Type:Article
Refereed:Yes
Divisions:Life Sciences > School of Chemistry, Food and Pharmacy > Department of Food and Nutritional Sciences
Interdisciplinary centres and themes > Institute for Cardiovascular and Metabolic Research (ICMR)
ID Code:12900
Uncontrolled Keywords:Parkinson's disease, neurodegeneration, flavonoid, polyphenol, hesperetin, pelargonidin, quercetin, catechin, caffeic acid, 5-S-cysteinyl-dopamine, DHBT-1, peroxynitrite, brain, dependent tyrosine nitration, mitochondrial complex i, induced, cell-death, nitric-oxide, cortical-neurons, oxidative metabolites, potential relevance, reaction pathways, l-cysteine, dopamine, Animals Cell Culture Techniques, Cell Survival/drug effects, Cells, Cultured Cerebral Cortex/cytology, Culture Media, Serum-Free Dopamine/*biosynthesis/chemistry, Flavonoids/*chemistry/pharmacology, Mice, Molecular Structure, Neurons/drug effects, Parkinson Disease/*etiology, Peroxynitrous Acid/*pharmacology, Phenols/*chemistry/pharmacology, Time Factors, Tryptamines/*biosynthesis/chemistry
Additional Information:G0400278/NI02/Medical Research Council/United Kingdom Research Support, Non-U.S. Gov't United States
Publisher:Elsevier

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