title: Vitiligo: a possible model of degenerative diseases.
abstract: Vitiligo is characterized by the progressive disappearance of pigment cells from skin and hair follicle. Several in vitro and in vivo studies show evidence of an altered redox status, suggesting that loss of cellular redox equilibrium might be the pathogenic mechanism in vitiligo. However, despite the numerous data supporting a pathogenic role of oxidative stress, there is still no consensus explanation underlying the oxidative stress-driven disappear of melanocytes from the epidermis. In this study, in vitro characterization of melanocytes cultures from non-lesional vitiligo skin revealed at the cellular level aberrant function of signal transduction pathways common with neurodegenerative diseases including modification of lipid metabolism, hyperactivation of mitogen-activated protein kinase (MAPK) and cAMP response element-binding protein (CREB), constitutive p53-dependent stress signal transduction cascades, and enhanced sensibility to pro-apoptotic stimuli. Notably, these long-term effects of subcytotoxic oxidative stress are also biomarkers of pre-senescent cellular phenotype. Consistent with this, vitiligo cells showed a significant increase in p16 that did not correlate with the chronological age of the donor. Moreover, vitiligo melanocytes produced many biologically active proteins among the senescence-associated secretory phenotype (SAPS), such as interleukin-6 (IL-6), matrix metallo proteinase-3 (MMP3), cyclooxygenase-2 (Cox-2), insulin-like growth factor-binding protein-3 and 7 (IGFBP3, IGFBP7). Together, these data argue for a complicated pathophysiologic puzzle underlying melanocytes degeneration resembling, from the biological point of view, neurodegenerative diseases. Our results suggest new possible targets for intervention that in combination with current therapies could correct melanocytes intrinsic defects.
authors.affiliation: Laboratory of Cutaneous Physiopathology, San Gallicano Dermatologic Institute, Istituto Di Ricovero e Cura a Carattere Scientifico, Rome, Italy. bellei@ifo.it
authors.forename: Barbara
authors.initials: B
authors.lastname: Bellei
authors.forename: Angela
authors.initials: A
authors.lastname: Pitisci
authors.forename: Monica
authors.initials: M
authors.lastname: Ottaviani
authors.forename: Matteo
authors.initials: M
authors.lastname: Ludovici
authors.forename: Carlo
authors.initials: C
authors.lastname: Cota
authors.forename: Fabiola
authors.initials: F
authors.lastname: Luzi
authors.forename: Maria Lucia
authors.initials: ML
authors.lastname: Dell'Anna
authors.forename: Mauro
authors.initials: M
authors.lastname: Picardo
mesh_terms: D000293:Adolescent; D000328:Adult; D017209:Apoptosis; D001706:Biopsy; D049109:Cell Proliferation; D002470:Cell Survival; D016922:Cellular Senescence; D002648:Child; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D004817:Epidermis / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D019084:Fluorescent Antibody Technique, Indirect; D006801:Humans; D007150:Immunohistochemistry; D008055:Lipids / Q000737:chemistry; D020935:MAP Kinase Signaling System; D008297:Male; D008544:Melanocytes / Q000166:cytology; D008875:Middle Aged; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D010641:Phenotype; D017382:Reactive Oxygen Species; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D014820:Vitiligo / Q000175:diagnosis* / Q000503:physiopathology*; D055815:Young Adult
chemical_list: D017362:Cyclic AMP Response Element-Binding Protein; D008055:Lipids; D017382:Reactive Oxygen Species; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53
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