Oxidative damage caused by free radicals produced during catecholamine autoxidation: Protective effects of O-methylation and melatonin

Joshua W. Miller, Jacob Selhub, James A. Joseph

Research output: Contribution to journalArticle

131 Scopus citations

Abstract

Catecholamine autoxidation produces reactive oxygen species that have been implicated in the loss of dopaminergic neurons in the nigrostriatal region of the brain that occurs during normal aging and in Parkinson's disease. In the present study, the potential protective effects of catecholamine O-methylation and of melatonin against catecholamine autoxidation-induced protein damage were assessed in vitro using the oxygen radical absorbance capacity (ORAC) assay. The rate of oxidation of the fluorescent protein porphyridium cruentum β-phycoerythrin (β-PE) caused by the oxidizing agent CuSO4 was shown to be accelerated by addition of the catecholamines dopamine and L-dopa. Replacement of dopamine and L-dopa in the assay with their O-methylated metabolites 3-O-methyldopamine and 3-O- methyldopa significantly decreased the rate of β-PE oxidation. When melatonin was added to the ORAC assay in combination with dopamine or L- dopa, the rate of β-PE oxidation was decreased as well. These findings were consistent with the following interpretations: (1) O-methylated catecholamines are less susceptible to autoxidation than their nonmethylated precursors, and (2) melatonin, which has recently been shown to be a powerful antioxidant, is capable of scavenging free radicals produced during catecholamine autoxidation. These findings suggest that O-methylation and melatonin may be important components of the brain's antioxidant defenses against catecholamine autoxidation and may protect against consequent dopaminergic neurodegeneration.

Original languageEnglish (US)
Pages (from-to)241-249
Number of pages9
JournalFree Radical Biology and Medicine
Volume21
Issue number2
DOIs
StatePublished - 1996
Externally publishedYes

Keywords

  • Autoxidation
  • Dopamine
  • Free radicals
  • L-Dopa
  • Melatonin
  • O-Methylation
  • Oxygen radical absorbance capacity (ORAC) assay
  • Parkinson's disease

ASJC Scopus subject areas

  • Medicine(all)
  • Toxicology
  • Clinical Biochemistry

Fingerprint Dive into the research topics of 'Oxidative damage caused by free radicals produced during catecholamine autoxidation: Protective effects of O-methylation and melatonin'. Together they form a unique fingerprint.

Cite this