title: Pheomelanin-induced oxidative stress: bright and dark chemistry bridging red hair phenotype and melanoma.
abstract: The complex interplay of genetic and epigenetic factors linking sun exposure to melanoma in the red hair phenotype hinges on the peculiar physical and chemical properties of pheomelanins and the underlying biosynthetic pathway, which is switched on by the effects of inactivating polymorphisms in the melanocortin 1 receptor gene. In addition to the long recognized UV-dependent pathways of toxicity and cell damage, a UV-independent pro-oxidant state induced by pheomelanin within the genetically determined background of the red hair phenotype has recently been disclosed. This review provides a detailed discussion of the possible UV-dependent and UV-independent chemical mechanisms underlying pheomelanin-mediated oxidative stress, with special reference to the oxygen-dependent depletion of glutathione and other cell antioxidants. The new concept of pheomelanin as a 'living' polymer and biocatalyst that may grow by exposure to monomer building blocks and may trigger autooxidative processes is also discussed. As a corollary, treatment of inflammatory skin diseases in RHP patients is briefly commented. Finally, possible concerted strategies for melanoma prevention in the red hair phenotype are proposed.
authors.affiliation: Department of Chemical Sciences, University of Naples 'Federico II', Naples, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Napolitano
authors.forename: Lucia
authors.initials: L
authors.lastname: Panzella
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Monfrecola
authors.forename: Marco
authors.initials: M
authors.lastname: d'Ischia
mesh_terms: D000818:Animals; D015972:Gene Expression Regulation, Neoplastic; D006200:Hair Color; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D008543:Melanins / Q000502:physiology*; D008545:Melanoma / Q000378:metabolism / Q000473:pathology*; D016877:Oxidants / Q000737:chemistry; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D010100:Oxygen / Q000737:chemistry; D010641:Phenotype; D017382:Reactive Oxygen Species / Q000378:metabolism; D044102:Receptor, Melanocortin, Type 1 / Q000235:genetics / Q000378:metabolism; D012867:Skin / Q000473:pathology; D012871:Skin Diseases / Q000378:metabolism / Q000473:pathology; D012878:Skin Neoplasms / Q000378:metabolism / Q000473:pathology*
chemical_list: D008543:Melanins; D016877:Oxidants; D017382:Reactive Oxygen Species; D044102:Receptor, Melanocortin, Type 1; C018362:pheomelanin; D010100:Oxygen
keywords: UV; glutathione; melanoma; oxidative stress; pheomelanin; reactive oxygen species; red hair