The GTPase-activating protein-related domain of neurofibromin interacts with MC1R and regulates pigmentation-mediated signaling in human melanocytes.

The melanocortin 1 receptor (MC1R) is a G-protein coupled receptor (GPCR) which plays a major role in controlling melanogenesis. A large body of evidence indicates that GPCRs are part of large protein complexes that are critical for their signal transduction properties. Among proteins which may affect MC1R signaling, neurofibromin (Nf1), a GTPase activating protein (GAP) for Ras, is of special interest as it regulates adenylyl cyclase activity and ERK signaling, two pathways involved in MC1R signaling. Moreover, mutations in this gene encoding Nf1 are responsible for neurofibromatosis type I, a disease inducing hyperpigmented flat skin lesions. Using co-immunoprecipitation and Bioluminescence Resonance Energy Transfer experiments we demonstrated a physical interaction of Nf1 with MC1R. In particular, the GAP domain of Nf1 directly and constitutively interacts with MC1R in melanocytes. Pharmacologic and genetic approaches revealed that the GAP activity of Nf1 is important to regulate intracellular signaling pathways involved in melanogenesis and, consequently, melanogenic enzyme expression and melanin production. These finding shed new light on the understanding and cure of skin pigmentation disorders.

Purple tulip extract improves signs of skin aging through dermal structural modulation as shown by genomic, protein expression and skin appearance of volunteers studied.

BACKGROUND: Purple tulip extract is a rich source of flavonoids which are powerful antioxidants and can hence be considered as an ideal candidate for use in skin care products. AIMS: We aimed to evaluate the effects of purple tulip extract on skin quality and to determine its molecular modes of interaction. METHODS: A pangenomic study on human skin fibroblasts was carried out to analyze multiple changes in gene expression. Ex vivo studies of human skin explants exposed to ultraviolet (UV) irradiation or H2 O2 were performed to assess modulations of protein expression. Finally, a clinical assay was carried out to evaluate the efficacy of purple tulip extract on skin appearance and condition of aged women. RESULTS: Genetic modulation analyses led us to infer the induction of many biological functions including cell differentiation, proliferation, migration, inflammatory responses, and matrix remodeling. The ex vivo studies revealed an enhancement of the collagen network and increased expression of glycosaminoglycans (GAG), fibronectin, and collagen VI. Finally, the clinical study highlighted the potential anti-aging properties of the purple tulip extract which decreased the relaxation of the oval face and improved skin elasticity after 28 days of treatment. Significant reductions of the length and depth of the nasolabial wrinkles were also observed. CONCLUSION: Our genomics data on the effect of purple tulip extract on the ex vivo UV-challenged skin showed that genes responsible for, among others, the upkeep of the skin, such as collagen induction, immune cell proliferation, and epidermal repair, were all up-regulated. More importantly, the clinical study corroborated these data by the visible and measurable effects of the topical purple tulip extract on the aged skin of 22 women, further demonstrating the beneficial impact of the extract on aged skin.