Cytotoxic and genotoxic potential of dopamine

Alan H. Stokes, Teresa G. Hastings, Kent Vrana

Research output: Contribution to journalShort survey

346 Scopus citations

Abstract

A variety of in vitro and in vivo studies demonstrate that dopamine is a toxic molecule that may contribute to neurodegenerative disorders such as Parkinson's disease and ischemia-induced striatal damage. While much attention has focused on the fact that the metabolism of dopamine produces reactive oxygen species (peroxide, superoxide, and hydroxyl radical), growing evidence suggests that the nenrotransmitter itself may play a direct role in the neurodegenerative process. Oxidation of the dopamine molecule produces a reactive quinone moiety that is capable of covalently modifying and damaging cellular macromolecules. This quinone formation occurs spontaneously, can be accelerated by metal ions (manganese or iron), and also arises from selected enzyme-catalyzed reactions. Macromolecular damage, combined with increased oxidant stress, may trigger cellular responses that eventually lead to cell death. Reactive quinones have long been known to represent environmental toxicants and, within the context of dopamine metabolism, may also play a role in pathological processes associated with neurodegeneration. The present discussion will review the oxidative metabolism of dopamine and describe experimental evidence suggesting that dopamine quinone may contribute to the cytotoxic and genotoxic potential of this essential neurotransmitter.

Original languageEnglish (US)
Pages (from-to)659-665
Number of pages7
JournalJournal of Neuroscience Research
Volume55
Issue number6
DOIs
StatePublished - Mar 15 1999

All Science Journal Classification (ASJC) codes

  • Cellular and Molecular Neuroscience

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