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

David Vauzour, Giulia Ravaioli, Katerina Vafeiadou, Ana Rodriguez-Mateos, Cristina Angeloni, Jeremy P E Spencer

Research output: Contribution to journalArticlepeer-review

100 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)145-51
Number of pages7
JournalArchives of biochemistry and biophysics
Volume476
Issue number2
DOIs
Publication statusPublished - 15 Aug 2008

Keywords

  • Animals
  • Cell Culture Techniques
  • Cell Survival
  • Cells, Cultured
  • Cerebral Cortex
  • Culture Media, Serum-Free
  • Dopamine
  • Flavonoids
  • Mice
  • Molecular Structure
  • Neurons
  • Parkinson Disease
  • Peroxynitrous Acid
  • Phenols
  • Polyphenols
  • Time Factors
  • Tryptamines

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