title: SIRT1 regulates MAPK pathways in vitiligo skin: insight into the molecular pathways of cell survival.
abstract: Vitiligo is an acquired and progressive hypomelanotic disease that manifests as circumscribed depigmented patches on the skin. The aetiology of vitiligo remains unclear, but recent experimental data underline the interactions between melanocytes and other typical skin cells, particularly keratinocytes. Our previous results indicate that keratinocytes from perilesional skin show the features of damaged cells. Sirtuins (silent mating type information regulation 2 homolog) 1, well-known modulators of lifespan in many species, have a role in gene repression, metabolic control, apoptosis and cell survival, DNA repair, development, inflammation, neuroprotection and healthy ageing. In the literature there is no evidence for SIRT1 signalling in vitiligo and its possible involvement in disease progression. Here, biopsies were taken from the perilesional skin of 16 patients suffering from non-segmental vitiligo and SIRT1 signalling was investigated in these cells. For the first time, a new SIRT1/Akt, also known as Protein Kinase B (PKB)/mitogen-activated protein kinase (MAPK) signalling has been revealed in vitiligo. SIRT1 regulates MAPK pathway via Akt-apoptosis signal-regulating kinase-1 and down-regulates pro-apoptotic molecules, leading to decreased oxidative stress and apoptotic cell death in perilesional vitiligo keratinocytes. We therefore propose SIRT1 activation as a novel way of protecting perilesional vitiligo keratinocytes from damage.
authors.affiliation: Department of Biochemical Sciences, University of Florence, Florence, Italy.
authors.forename: Matteo
authors.initials: M
authors.lastname: Becatti
authors.forename: Claudia
authors.initials: C
authors.lastname: Fiorillo
authors.forename: Victoria
authors.initials: V
authors.lastname: Barygina
authors.forename: Cristina
authors.initials: C
authors.lastname: Cecchi
authors.forename: Torello
authors.initials: T
authors.lastname: Lotti
authors.forename: Francesca
authors.initials: F
authors.lastname: Prignano
authors.forename: Agrippino
authors.initials: A
authors.lastname: Silvestro
authors.forename: Paolo
authors.initials: P
authors.lastname: Nassi
authors.forename: Niccolò
authors.initials: N
authors.lastname: Taddei
mesh_terms: D000107:Acetylation / Q000187:drug effects; D000328:Adult; D000975:Antioxidants / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D015237:Dinoprost / Q000031:analogs & derivatives / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D015603:Keratinocytes / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D048848:MAP Kinase Kinase Kinase 5 / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008875:Middle Aged; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases; D018384:Oxidative Stress / Q000187:drug effects; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D000077185:Resveratrol; D056564:Sirtuin 1 / Q000378:metabolism*; D012867:Skin / Q000201:enzymology* / Q000473:pathology; D013267:Stilbenes / Q000494:pharmacology; D013481:Superoxides / Q000378:metabolism; D014820:Vitiligo / Q000201:enzymology* / Q000473:pathology
chemical_list: D000975:Antioxidants; D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species; D013267:Stilbenes; D013481:Superoxides; C075750:8-epi-prostaglandin F2alpha; D015237:Dinoprost; D051057:Proto-Oncogene Proteins c-akt; D020928:Mitogen-Activated Protein Kinases; D048848:MAP Kinase Kinase Kinase 5; C482858:MAP3K5 protein, human; D053148:Caspase 3; C447939:SIRT1 protein, human; D056564:Sirtuin 1; D000077185:Resveratrol
keywords: Akt; MAPK; SIRT1; oxidative stress; vitiligo