Ectopic deposition of melanin pigments as detoxifying mechanism: a paradigm for basal nuclei pigmentation.
Melanins are UV shielding pigments found in skin and other light exposed tissues. However, a kind of melanin, named neuromelanin (NM), is found in those deep brain loci that degenerate in Parkinson's disease (PD), where no such a function may be imagined. The NM synthetic pathway, different from the one of eumelanin based on tyrosinase, is still obscure as well as its physiological function. Here we show that under conditions of excess of toxic quinone concentration, nonmelanocytic cell strains (i.e., primary keratinocytes) may accumulate a dark cytoplasmatic pigment that proved to be a melanin. The ability of pigment deposition, possibly driven by peroxidases, is restricted to diploid cells and increases cell survival acting as a sink for potentially hazardous quinones. We suggest that in the basal nuclei, exposed to high level of catecholaminergic neurotransmitters, NM deposition is a relevant antioxidant mechanism by trapping quinones and semiquinones, thus protecting neurons from accumulating damage over many years. In this perspective, just as a hypothesis, we may imagine that PD neuron degeneration is the consequence of a reduced/abrogated ability to produce neuromelanin.
De Marco
Federico
F
Laboratory of Virology, "Regina Elena Institute for Cancer Research", Via delle Messi d'Oro, 156-00156 Rome, Italy.
Foppoli
Cesira
C
Coccia
Raffaella
R
Blarzino
Carla
C
Perluigi
Marzia
M
Cini
Chiara
C
Marcante
Maria Luisa
ML
D000975:Antioxidants / Q000737:chemistry; D015152:Blotting, Northern; D002455:Cell Division; D002460:Cell Line; D002470:Cell Survival; D002478:Cells, Cultured; D003593:Cytoplasm / Q000378:metabolism; D005559:Formamides / Q000494:pharmacology; D005979:Glutathione Peroxidase / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D015603:Keratinocytes / Q000378:metabolism; D008543:Melanins / Q000737:chemistry* / Q000378:metabolism; D008956:Models, Chemical; D010300:Parkinson Disease / Q000378:metabolism; D010544:Peroxidases / Q000378:metabolism; D012313:RNA / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism; D013765:Tetrahydropapaveroline / Q000737:chemistry / Q000494:pharmacology; D013997:Time Factors; D014162:Transfection; D014466:Ultraviolet Rays
D000975:Antioxidants; D005559:Formamides; D008543:Melanins; D012333:RNA, Messenger; C014121:neuromelanin; D013765:Tetrahydropapaveroline; C031066:formamide; D012313:RNA; D010544:Peroxidases; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase