Membrane lipid alterations as a possible basis for melanocyte degeneration in vitiligo.
The occurrence of oxidative stress has been proposed as a pathogenetic mechanism for melanocyte degeneration in vitiligo. In order to evaluate this possible correlation we focused on the lipid component of cell membranes. We observed in vitiligo melanocytes, through FACS methods, an increased median fluorescence intensity of rhodamine 123 and C11-BODIPY581/591 indicating a spontaneous higher production of reactive oxygen species (ROS) and membrane lipoperoxidation, associated with an altered pattern of cardiolipin (CL) distribution, defined on the basis of the fluorescence pattern after staining with 10-nonyl acridine orange. We confirmed membrane peroxidation by confocal and contrast-phase microscopes and demonstrated impaired activity of the mitochondrial electron transport chain (ETC) complex I. Finally, we observed increased apoptotic events following exposure to the pro-oxidant cumene hydroperoxide by Annexin V/propidium iodide fluorescence. We hypothesize that in vitiligo melanocytes lipid instability, with a defect in the synthesis or recycling of CL, induces ETC impairment and ROS production. In basal conditions melanocytes maintain the redox balance whereas following chemical or physical stress ROS-mediated membrane peroxidation is increased with a possible further CL oxidation, leading to cell death or detachment.
Dell'Anna
Maria Lucia
ML
Laboratory of Cutaneous Physiopathology, IRCCS, Rome, Italy.
Ottaviani
Monica
M
Albanesi
Veronica
V
Vidolin
Andrea Paro
AP
Leone
Giovanni
G
Ferraro
Carmela
C
Cossarizza
Andrea
A
Rossi
Luisa
L
Picardo
Mauro
M
D017209:Apoptosis / Q000187:drug effects; D001555:Benzene Derivatives / Q000494:pharmacology; D001706:Biopsy; D002308:Cardiolipins / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D042967:Electron Transport Complex I / Q000502:physiology; D006801:Humans; D015227:Lipid Peroxidation / Q000502:physiology*; D008544:Melanocytes / Q000473:pathology* / Q000502:physiology; D008563:Membrane Lipids / Q000502:physiology*; D016877:Oxidants / Q000494:pharmacology; D018384:Oxidative Stress / Q000502:physiology; D017382:Reactive Oxygen Species / Q000378:metabolism; D012867:Skin / Q000473:pathology; D014820:Vitiligo / Q000473:pathology* / Q000503:physiopathology
D001555:Benzene Derivatives; D002308:Cardiolipins; D008563:Membrane Lipids; D016877:Oxidants; D017382:Reactive Oxygen Species; D042967:Electron Transport Complex I; C007164:cumene hydroperoxide