Peroxynitrite induced formation of the neurotoxins 5-S-cysteinyl-dopamine and DHBT-1: implications for Parkinson's disease and protection by polyphenols.
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| Abstract |
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 microM) 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.
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| Authors | David Vauzour, Giulia Ravaioli, Katerina Vafeiadou, Ana Rodriguez-Mateos, Cristina Angeloni, Jeremy P E Spencer |
| Journal | Archives of biochemistry and biophysics (Arch Biochem Biophys) Vol. 476 Issue 2 Pg. 145-51 (Aug 15 2008) ISSN: 1096-0384 [Electronic] United States |
| PMID | 18394421 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't) |
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