title: Reverse Engineering Applied to Red Human Hair Pheomelanin Reveals Redox-Buffering as a Pro-Oxidant Mechanism.
abstract: Pheomelanin has been implicated in the increased susceptibility to UV-induced melanoma for people with light skin and red hair. Recent studies identified a UV-independent pathway to melanoma carcinogenesis and implicated pheomelanin's pro-oxidant properties that act through the generation of reactive oxygen species and/or the depletion of cellular antioxidants. Here, we applied an electrochemically-based reverse engineering methodology to compare the redox properties of human hair pheomelanin with model synthetic pigments and natural eumelanin. This methodology exposes the insoluble melanin samples to complex potential (voltage) inputs and measures output response characteristics to assess redox activities. The results demonstrate that both eumelanin and pheomelanin are redox-active, they can rapidly (sec-min) and repeatedly redox-cycle between oxidized and reduced states, and pheomelanin possesses a more oxidative redox potential. This study suggests that pheomelanin's redox-based pro-oxidant activity may contribute to sustaining a chronic oxidative stress condition through a redox-buffering mechanism.
authors.affiliation: Institute for Biosystems and Biotechnology Research University of Maryland 5115 Plant Sciences Building College Park, MD 20742, USA.|Fischell Department of Bioengineering University of Maryland College Park, MD 20742, USA.
authors.forename: Eunkyoung
authors.initials: E
authors.lastname: Kim
authors.affiliation: Department of Chemical Sciences, University of Naples Federico II, Via Cintia 4, I-80126 Naples (Italy).
authors.forename: Lucia
authors.initials: L
authors.lastname: Panzella
authors.affiliation: Department of Chemical Sciences, University of Naples Federico II, Via Cintia 4, I-80126 Naples (Italy).|Department of Clinical Medicine and Surgery, University of Naples "Federico II" - Via Pansini 5, I-80131 Naples, Italy.
authors.forename: Raffaella
authors.initials: R
authors.lastname: Micillo
authors.affiliation: Institute for Biosystems and Biotechnology Research University of Maryland 5115 Plant Sciences Building College Park, MD 20742, USA.|Fischell Department of Bioengineering University of Maryland College Park, MD 20742, USA.
authors.forename: William E
authors.initials: WE
authors.lastname: Bentley
authors.affiliation: Department of Chemical Sciences, University of Naples Federico II, Via Cintia 4, I-80126 Naples (Italy).
authors.forename: Alessandra
authors.initials: A
authors.lastname: Napolitano
authors.affiliation: Institute for Biosystems and Biotechnology Research University of Maryland 5115 Plant Sciences Building College Park, MD 20742, USA.|Fischell Department of Bioengineering University of Maryland College Park, MD 20742, USA.
authors.forename: Gregory F
authors.initials: GF
authors.lastname: Payne
mesh_terms: D006197:Hair / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D008543:Melanins / Q000737:chemistry* / Q000378:metabolism; D008956:Models, Chemical; D010084:Oxidation-Reduction / Q000528:radiation effects; D010858:Pigmentation; D014466:Ultraviolet Rays
chemical_list: D008543:Melanins; C018362:pheomelanin