title: Red human hair pheomelanin is a potent pro-oxidant mediating UV-independent contributory mechanisms of melanomagenesis.
abstract: The highest incidence of melanoma in red haired individuals is attributed to the synthesis and phototoxic properties of pheomelanin pigments. Recently, pheomelanin has also been implicated in UV-independent pathways of oxidative stress; however, the underlying mechanisms have remained uncharted. Herein, we disclose the unprecedented property of purified red human hair pheomelanin (RHP) to promote (i) the oxygen-dependent depletion of major cell antioxidants, for example glutathione and NADH; (ii) the autoxidative formation of melanin pigments from their precursors. RHP would thus behave as a unique 'living' polymer and biocatalyst that may grow by simple exposure to monomer building blocks and may trigger autoxidative processes. These results yield new clues as to the origin of the pro-oxidant state in the red hair phenotype, uncover non-enzymatic pathways of melanogenesis, and pave the way to innovative strategies for melanoma prevention.
authors.affiliation: Department of Chemical Sciences, University of Naples Federico II, Naples, Italy.
authors.forename: Lucia
authors.initials: L
authors.lastname: Panzella
authors.forename: Loredana
authors.initials: L
authors.lastname: Leone
authors.forename: Giorgia
authors.initials: G
authors.lastname: Greco
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Vitiello
authors.forename: Gerardino
authors.initials: G
authors.lastname: D'Errico
authors.forename: Alessandra
authors.initials: A
authors.lastname: Napolitano
authors.forename: Marco
authors.initials: M
authors.lastname: d'Ischia
mesh_terms: D053898:Biosynthetic Pathways / Q000528:radiation effects; D063646:Carcinogenesis / Q000378:metabolism / Q000473:pathology* / Q000528:radiation effects; D004578:Electron Spin Resonance Spectroscopy; D005978:Glutathione / Q000378:metabolism; D006200:Hair Color; D006801:Humans; D008543:Melanins / Q000096:biosynthesis / Q000378:metabolism*; D008545:Melanoma / Q000378:metabolism* / Q000473:pathology*; D008954:Models, Biological; D009243:NAD / Q000378:metabolism; D016877:Oxidants / Q000378:metabolism*; D010084:Oxidation-Reduction / Q000528:radiation effects; D014466:Ultraviolet Rays
chemical_list: D008543:Melanins; D016877:Oxidants; C018362:pheomelanin; D009243:NAD; C041877:eumelanin; D005978:Glutathione
keywords: glutathione; melanin precursors; melanoma; pheomelanin; pro-oxidant; redhair