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 language | English |
|---|---|
| Pages (from-to) | 145-51 |
| Number of pages | 7 |
| Journal | Archives of biochemistry and biophysics |
| Volume | 476 |
| Issue number | 2 |
| DOIs | |
| Publication status | Published - 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