title: Oxidative damage caused by free radicals produced during catecholamine autoxidation: protective effects of O-methylation and melatonin.
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 beta-phycoerythrin (beta-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 beta-PE oxidation. When melatonin was added to the ORAC assay in combination with dopamine or L-dopa, the rate of beta-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.
authors.affiliation: Vitamin Bioavailability Laboratory, Jean Mayer, USDA Human Nutrition Research Center on Aging, Tufts University, USA.
authors.forename: J W
authors.initials: JW
authors.lastname: Miller
authors.forename: J
authors.initials: J
authors.lastname: Selhub
authors.forename: J A
authors.initials: JA
authors.lastname: Joseph
mesh_terms: D002395:Catecholamines / Q000378:metabolism*; D019327:Copper Sulfate / Q000737:chemistry; D003846:Deoxyepinephrine / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism / Q000494:pharmacology; D005609:Free Radicals; D007980:Levodopa / Q000378:metabolism / Q000494:pharmacology; D008550:Melatonin / Q000494:pharmacology*; D008745:Methylation; D010084:Oxidation-Reduction; D010799:Phycoerythrin / Q000031:analogs & derivatives / Q000378:metabolism; D013050:Spectrometry, Fluorescence; D014443:Tyrosine / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: D002395:Catecholamines; D005609:Free Radicals; D010799:Phycoerythrin; D014443:Tyrosine; D007980:Levodopa; D008550:Melatonin; D019327:Copper Sulfate; D003846:Deoxyepinephrine; C008404:3-methoxytyrosine; D004298:Dopamine