Oral communication, PS4 / C41

Official XXIst International Pigment Cell Conference website - 21-24 Sept 2011, Bordeaux - France | updated: September 04 2011

Pheomelanin is a prooxidant promoting DOPA conversion to a eumelanin coating: discovery of a non-enzymatic mimic of the natural casing process of melanosome assembly

According to a currently accepted kinetic model, assembly of pigment-containing organelles, the melanosomes, occurs by a casing process in which a pheomelanin core is initially formed and is then encapsulated into a eumelanin coating. Photoemission electron microscopy imaging studies of iridial melanosomes and neuromelanin granules showed eumelanin-type surface properties despite a large pheomelanin content. The present study aimed at probing the oxidation reactivity of pheomelanin to address at chemical level the mechanisms underlying the growth of eumelanin shell onto the pheomelanin core. Oxidation of dopa and other eumelanin precursors at 1 mM concentration in air-equilibrated phosphate buffer at pH 7.4 in the presence of 20% (w/w) 5-S-cysteinyldopa melanin (CD-melanin) is followed by HPLC analysis. The resulting dark pigment is analyzed by scanning electron microscopy (SEM) and chemical degradation. The rate of aerial oxidation of a series of catecholamines including DOPA is markedly increased in the presence of CD-melanin, leading to dark insoluble eumelanin-like polymers. SEM analysis indicated a close similarity of the morphology of the resulting pigment with that of a pure DOPA-melanin sample suggesting encasing of the CD-melanin component into the DOPA-melanin coating. Chemical degradation experiments indicated that while most of the CD-melanin was readily solubilized and released from the filter by alkaline washings, no CD-melanin was detected in the washings of the DOPA melanin-coated sample, confirming the presence of an insoluble DOPA-melanin coating preventing solubilization of the pheomelanin pigment during the washing steps. In conclusion, synthetic pheomelanin from CD is capable of accelerating the aerial polymerization of DOPA to give eumelanin-like deposits that encapsulate the pheomelanic core and gradually quench the redox centers. The oxidative polymerization process is likely mediated by key benzothiazine units through a redox interaction mechanism occurring on the surface of the finely suspended pro-oxidant polymer. These results disclose a non-enzymatic process mimicking the natural casing model of melanin synthesis which may be relevant to the origin of the casing architecture in the neuromelanin of human substantia nigra which apparently lacks enzymatic systems for catecholamine oxidation and deposition onto the pheomelanin-like core.

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