Peroxynitrite induced formation of the neurotoxins 5-S-cysteinyl-dopamine and DHBT-1: implications for Parkinson's disease and protection by polyphenols.
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.
Vauzour
David
D
Molecular Nutrition Group, School of Chemistry, Food and Pharmacy, The University of Reading, P.O. Box 226, Whiteknights Campus, Reading RG6 6AP, UK.
Ravaioli
Giulia
G
Vafeiadou
Katerina
K
Rodriguez-Mateos
Ana
A
Angeloni
Cristina
C
Spencer
Jeremy P E
JP
D000818:Animals; D018929:Cell Culture Techniques; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D016895:Culture Media, Serum-Free; D004298:Dopamine / Q000096:biosynthesis* / Q000737:chemistry; D005419:Flavonoids / Q000737:chemistry* / Q000494:pharmacology; D051379:Mice; D015394:Molecular Structure; D009474:Neurons / Q000187:drug effects; D010300:Parkinson Disease / Q000209:etiology*; D030421:Peroxynitrous Acid / Q000494:pharmacology*; D010636:Phenols / Q000737:chemistry* / Q000494:pharmacology; D059808:Polyphenols; D013997:Time Factors; D014363:Tryptamines / Q000096:biosynthesis* / Q000737:chemistry
D016895:Culture Media, Serum-Free; D005419:Flavonoids; D010636:Phenols; D059808:Polyphenols; D014363:Tryptamines; C076856:5,5'-dihydroxy-4,4'-bitryptamine; D030421:Peroxynitrous Acid; D004298:Dopamine