title: Membrane lipid defects are responsible for the generation of reactive oxygen species in peripheral blood mononuclear cells from vitiligo patients.
abstract: The pathogenesis of vitiligo, an acquired depigmenting disease of the skin, involves oxidative stress. Based on that, the generation of reactive oxygen species (ROS) by the mitochondria may be relevant in the pathogenesis of vitiligo. Here, we evaluate the biochemical and functional alterations involved in the defective activity that has been previously described both in melanocytes and peripheral blood mononuclear cells (PBMC) from vitiligo patients. Moreover, we used a freeze-thaw test as a mild stress stimulus to disclose any latent defects in the assembly of membrane lipids that may compromise the functionality of the membrane itself. We show that the lipid constitution of the membrane is altered in vitiligo. Specifically, the cardiolipin (CL) level in the mitochondrial inner membrane is reduced and the level of cholesterol is increased. Furthermore, an increase in the expression level of 3-hydroxy-3methyl-glutaryl-CoenzymeA-reductase (HMG-CoA reductase), the rate-limiting enzyme for cholesterol biosynthesis, was also seen. Associated with that, the expression of electron transport chain (ETC) lipid-dependent subunits was also modified, and their expression was further affected by the freeze-thaw stress. The expression of CL-independent mitochondrial proteins, such as porin and Bcl2, were unaffected in vitiligo PBMC. These data confirm that ETC protein expression mainly correlates with lipid arrangement and that loss of their expression is not due to generalized or random oxidative-mediated damage. We suggest that the modification of membrane lipid components in vitiligo cells may be the biochemical basis for the mitochondrial impairment and the subsequent production of intracellular ROS following the exposure to a mild stress.
authors.affiliation: Laboratory of Cutaneous Physiopathology, San Gallicano Dermatological Institute, IRCCS, Rome, Italy. mldellanna@libero.it
authors.forename: Maria Lucia
authors.initials: ML
authors.lastname: Dell'Anna
authors.forename: Monica
authors.initials: M
authors.lastname: Ottaviani
authors.forename: Barbara
authors.initials: B
authors.lastname: Bellei
authors.forename: Veronica
authors.initials: V
authors.lastname: Albanesi
authors.forename: Andrea
authors.initials: A
authors.lastname: Cossarizza
authors.forename: Luisa
authors.initials: L
authors.lastname: Rossi
authors.forename: Mauro
authors.initials: M
authors.lastname: Picardo
mesh_terms: D000328:Adult; D002308:Cardiolipins / Q000378:metabolism; D016022:Case-Control Studies; D002784:Cholesterol / Q000378:metabolism; D045222:Electron Transport Chain Complex Proteins / Q000378:metabolism; D005260:Female; D005615:Freezing; D006801:Humans; D006903:Hydroxymethylglutaryl CoA Reductases / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000378:metabolism* / Q000473:pathology; D015227:Lipid Peroxidation; D008297:Male; D008563:Membrane Lipids / Q000378:metabolism*; D008875:Middle Aged; D008928:Mitochondria / Q000378:metabolism* / Q000473:pathology; D051336:Mitochondrial Membranes / Q000378:metabolism; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism*; D014820:Vitiligo / Q000097:blood / Q000378:metabolism* / Q000473:pathology; D055815:Young Adult
chemical_list: D002308:Cardiolipins; D045222:Electron Transport Chain Complex Proteins; D008563:Membrane Lipids; D017382:Reactive Oxygen Species; D002784:Cholesterol; D006903:Hydroxymethylglutaryl CoA Reductases