Agouti Protein Can Act Independently of Melanocyte-Stimulating Hormone to Inhibit Melanogenesis

Hunt, Gillian; Thody, AJ

doi:10.1677/joe.0.147r001

Cited by 42 publications

(23 citation statements)

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“…Em melanócitos humanos normais, onde o número de MC1-R expresso é relativamente baixo, ASP anula completamente os efeitos estimulatórios de α-MSH na proliferação melanocítica e melanogênese. 17,25,53 A incapacidade de se bronzear nos indivíduos com variação no MC1-R é consistente, com um papel crítico para o MSH/AMPc nesta resposta, mas alguns estudos indicam que o dano ao DNA do melanócito pode mediar a pigmentação induzida por RUV. 54 FIGURA 6: Esquema da sinalização do α-MSH via MC1-R, resultando na formação de eumelanina e feomelanina Fonte: Thody AJ, et al 20 …”

Section: Melaninaunclassified

Fisiopatologia do melasma

Miot¹,

Miot²,

Silva³

et al. 2009

An. Bras. Dermatol.

125

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Resumo: Melasma é uma dermatose comum que cursa com alteração da cor da pele normal, resultante da hiperatividade melanocítica focal epidérmica de clones de melanócitos hiperfuncionantes, com consequente hiperpigmentação melânica induzida, principalmente, pela radiação ultravioleta. Clinicamente, caracteriza-se por manchas acastanhadas, localizadas preferencialmente na face, embora possa acometer também região cervical, torácica anterior e membros superiores. Mulheres em período fértil e de fototipos intermediários representam as populações mais acometidas. Grande parte de sua fisiopatogenia permanece desconhecida, havendo relação com fatores genéticos, hormonais, uso de medicamentos, cosméticos, endocrinopatias e fotoexposição. Os autores discutem os principais elementos relacionados à pigmentação da pele e ao desenvolvimento do melasma. Palavras-chave: Melanose; Pigmentação da pele; Raios Ultravioleta; Transtornos da pigmentação Abstract: Melasma is a common dermatosis that involves changes in normal skin pigmentation, resulting from the hyperactivity of epidermal melanocytes. The consequent hyperpigmentation is mostly induced by ultraviolet radiation. Clinically, melasma is characterized by light to dark brown macules that usually occur on the face, although they can also affect the cervical and anterior thoracic regions and upper members. Fertile age women and those with intermediate skin phototypes are most likely to develop melasma. Most of its physiopathogenics is not yet fully understood, but there is a relation with genetic and hormonal factors, drugs and cosmetics use, endocrinopathies and sun exposure. The authors discuss the main aspects associated with skin pigmentation and the development of melasma.

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Section: Melaninaunclassified

Fisiopatologia do melasma

Miot¹,

Miot²,

Silva³

et al. 2009

An. Bras. Dermatol.

125

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“…ASP is an antagonist of the melanocortin 1 receptor, which plays a key role in regulating pigmentation (21). ASP inhibits melanin formation in mouse melanocytes and in melanoma cells as well as in NHM (22)(23)(24). We treated NHM obtained from neonatal moderately pigmented (n-MP) skin with ASP.…”

Section: Sox9 Is Expressed In Melanocytes In Vivomentioning

confidence: 99%

“…However, we also found a decrease in SOX9 expression after treatment with ASP. Interestingly, ASP is known to decrease pigmentation in mouse and human melanocytes (22)(23)(24)(25). Transfection of the ASP gene in the skin and hair follicles of rats decreases tyrosinase expression and pigmentation (38).…”

Section: Figmentioning

confidence: 99%

SOX9 is a key player in ultraviolet B-induced melanocyte differentiation and pigmentation

Passeron

Valencia

Bertolotto

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

121

115

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SOX (SRY type HMG box) proteins are transcription factors that are predominantly known for their roles during development. During melanocyte development from the neural crest, SOX10 regulates microphthalmia-associated transcription factor, which controls a set of genes critical for pigment cell development and pigmentation, including dopachrome tautomerase and tyrosinase. We report here that another SOX factor, SOX9, is expressed by melanocytes in neonatal and adult human skin and is up-regulated by UVB exposure. We demonstrate that this regulation is mediated by cAMP and protein kinase. We also show that agouti signal protein, a secreted factor known to decrease pigmentation, down-regulates SOX9 expression. In adult and neonatal melanocytes, SOX9 regulates microphthalmia-associated transcription factor, dopachrome tautomerase, and tyrosinase promoters, leading to an increase in the expression of these key melanogenic proteins and finally to a stimulation of pigmentation. SOX9 completes the complex and tightly regulated process leading to the production of melanin by acting at a very upstream level. This role of SOX9 in pigmentation emphasizes the poorly understood impact of SOX proteins in adult tissues.microphthalmia-associated transcription factor ͉ tyrosinase ͉ protein kinase A ͉ melanocyte-stimulating hormone ͉ agouti signal protein S ox (SRY type HMG box) proteins are transcription factors that belong to the HMG box superfamily of DNA-binding proteins and play a key role during development. SOX9 belongs to the SOX-E subgroup, which includes SOX8, SOX9, and SOX10. The structures of these proteins show a high conservation and similar positions of their HMG boxes (1). SOX10 has been shown to play a key role in the regulation of melanocyte differentiation (2), and mutations in SOX10 lead to Waardenburg syndrome type 4, a genetic hypomelanosis with deafness and megacolon (3). During melanocyte development from the neural crest, SOX10 regulates the expression of microphthalmia-associated transcription factor (MITF), which in turn controls a set of genes critical for pigment cell development and pigmentation (4). Indeed, in conjunction with other transcription factors, MITF regulates dopachrome tautomerase (DCT), tyrosinase (the limiting enzyme for melanogenesis), and tyrosinase-related protein 1 (TYRP1). All of these proteins are essential for the full differentiation of melanocytes and are directly involved in melanin synthesis. SOX10 also acts as a critical transactivator of DCT, which MITF, on its own, is insufficient to stimulate (5-7).SOX9 has a key role in sexual determination and chondrogenesis, and mutations in SOX9 can lead to campomelic dysplasia, a skeletal dysmorphology associated in most XY cases with sex reversal (8, 9). During embryonic development, the SOX9 gene becomes active in all prechondrocytic mesenchymal condensations, and its expression is maintained at high levels in fully differentiated chondrocytes. The direct target for SOX9 is a chondrocyte-specific enhancer in the gene for collagen ...

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“…After treatment, cells (1 × 10 6 ) were lysed to measure melanin levels using the method of Hunt (18), and the production of chromogen measured by absorption spectrophotometry at 400 nm.…”

Section: Quantification Of Melaninmentioning

confidence: 99%