Tyrosinase enhances the covalent modification of DNA by dopamine

Alan H. Stokes, Buddy G. Brown, Chin K. Lee, David J. Doolittle, Kent E. Vrana

Research output: Contribution to journalArticlepeer-review

27 Scopus citations

Abstract

Dopamine-induced DNA damage was studied in vitro in the presence of the enzyme tyrosinase. Dopamine autoxidizes to form dopamine quinone, a reactive molecule which spontaneously decomposes to form additional reactive species that can modify cellular macromolecules. The conversion of dopamine to reactive dopamine quinone is accelerated by the enzyme tyrosinase. The objective of this study was to evaluate whether dopamine autoxidation would lead to DNA-reactive intermediates and whether tyrosinase would increase the rate of this reaction. Incubation of DNA with [3H]dopamine resulted in the concentration-dependent covalent incorporation of the labeled catecholamine into precipitable nucleic acid (DNA adduct formation). The presence of tyrosinase increased the incorporation by as much as two orders of magnitude. Antioxidants markedly reduced this incorporation, suggesting that dopamine free-radicals were critical in DNA modification. DNA adducts formed by dopamine in the presence of tyrosinase were visualized using 32P-postlabeling and thin layer chromatography. The results suggest that DNA modification by dopamine is accelerated by tyrosinase which, in turn, could contribute to destruction of dopaminergic neurons in vivo.

Original languageEnglish (US)
Pages (from-to)167-170
Number of pages4
JournalMolecular Brain Research
Volume42
Issue number1
DOIs
StatePublished - Nov 1996

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cellular and Molecular Neuroscience

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