Radical sequestration by protein-bound 3,4-dihydroxyphenylalanine

Michelle Nelson, Alice R. Foxwell, Peter Tyrer, Roger T. Dean

    Research output: Contribution to journalArticle

    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.
    Original languageEnglish
    Number of pages7
    JournalInternational Journal of Biochemistry and Cell Biology
    DOIs
    Publication statusPublished - 2010

    Open Access - Access Right Statement

    ©2010

    Keywords

    • antioxidants
    • oxidation
    • oxidative stress
    • proteins
    • radical scavenging

    Fingerprint

    Dive into the research topics of 'Radical sequestration by protein-bound 3,4-dihydroxyphenylalanine'. Together they form a unique fingerprint.

    Cite this