title: Radical sequestration by protein-bound 3,4-dihydroxyphenylalanine.
abstract: Protein-bound 3,4-dihydroxyphenylalanine (PB-DOPA), a redox-active product of protein oxidation, is capable of functioning as both a pro- and antioxidant. A number of in vitro and in vivo studies have demonstrated a toxic, non-toxic or even beneficial effect of free DOPA, however little investigation has examined the physiological activity of PB-DOPA. Being the major treatment available for Parkinson's disease, most studies have focused on the effect of DOPA within neurological cells or tissues, although the presence of PB-DOPA in other locations, for example within atherosclerotic plaques, suggests that broader research is needed to fully understand the physiological effects of both free and PB-DOPA. We hypothesise that the generation of PB-DOPA can trigger an enhancement of the cellular antioxidant defence system, thus enabling PB-DOPA to restrict and potentially terminate the initiating oxidative stress, minimising the level of oxidative damage. Using luminol-enhanced chemiluminescence, we demonstrate that free DOPA is capable of direct peroxyl radical scavenging, even in the presence of competing scavengers, and has a different effect to that of the parent amino acid, tyrosine. Furthermore, we show that both free and PB-DOPA, in combination or individually, were able to protect monocytes and macrophages from peroxyl radical-induced oxidative stress in vitro. These results confirm a role for both free and PB-DOPA in cellular antioxidant defences and suggest the possibility of using DOPA as a potential therapeutic for the treatment of diseases involving oxidative stress or the accumulation of oxidative damage.
authors.affiliation: Faculty of Applied Science, University of Canberra, Canberra, ACT 2601, Australia. michelle.nelson@canberra.edu.au
authors.forename: Michelle
authors.initials: M
authors.lastname: Nelson
authors.forename: A Ruth
authors.initials: AR
authors.lastname: Foxwell
authors.forename: Peter
authors.initials: P
authors.lastname: Tyrer
authors.forename: Roger T
authors.initials: RT
authors.lastname: Dean
mesh_terms: D000578:Amidines / Q000633:toxicity; D000818:Animals; D050197:Atherosclerosis / Q000517:prevention & control; D002454:Cell Differentiation; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D019610:Cytoprotection / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D016166:Free Radical Scavengers / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D007980:Levodopa / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D049408:Luminescent Agents; D051379:Mice; D009000:Monocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D016877:Oxidants / Q000633:toxicity; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects*; D021381:Protein Transport; D011506:Proteins / Q000737:chemistry / Q000378:metabolism*; D014443:Tyrosine / Q000737:chemistry
chemical_list: D000578:Amidines; D016166:Free Radical Scavengers; D049408:Luminescent Agents; D016877:Oxidants; D011506:Proteins; D014443:Tyrosine; D007980:Levodopa; C046728:2,2'-azobis(2-amidinopropane)