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.

SIRT1 activity is decreased in lesional psoriatic skin

“…SIRT1 activity was assessed using SIRT1 Direct Fluorescent Screening Assay Kit (Cayman, Ann Arbor, MI, USA) as previously described [4]. Compared with fibroblasts from healthy subjects, psoriatic cells exhibit a marked decrease (325.8 ± 58.42 vs 724.3 ± 123.9, p \ 0.0001) in SIRT1 activity.…”

DermaGene and VitmiRS: a comprehensive systems analysis of genetic dermatological disorders

“…Increased expression of miR-9 downregulates SIRT1 resulting in melanocytes apoptosis in vitiligo (Saunders et al 2010). SIRT1 has been shown to regulate stress-activated MAPK pathway via Akt and ASK1 in vitiligo keratinocytes (Becatti et al 2014). Previous studies have demonstrated the influence of miR-145 on the genes involved in the pigmentation process (Dynoodt et al 2013).…”

Protection of coronary endothelial cells from cigarette smoke-induced oxidative stress by a new MnII-containing polyamine-polycarboxilate scavenger of superoxide anion

“…Mitochondrial membrane potential was assessed as previously reported [24] using tetramethylrhodamine methyl ester perchlorate (TMRM), a lipophilic potentiometric fluorescent dye that distributes between the mitochondria and cytosol in proportion to Δψ by virtue of its positive charge. At low concentrations, the fluorescence intensity depends on dye accumulation in mitochondria, which in turn is directly related to mitochondrial potential.…”