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SFRP5 inhibits melanin synthesis of melanocytes in vitiligo by suppressing the Wnt/b-catenin signaling

Genes & Diseases 2021年第5期8卷 677-688页

作者： Daopei Zou Yangmei Chen Lingzhao Zhang Xiaohui Yuan Yujie Zhang Adelina Inggawati Pham Thi Kieu Nguyet Tianwen Gao Jin Chen Department of Dermatology The First Affiliated Hospital of Chongqing Medical UniversityChongqing400010PR China Key Laboratory of Clinical Laboratory Diagnostics Ministry of EducationChongqing Medical UniversityChongqing400016PR China Department of Dermatology Xijing HospitalFourth Military Medical UniversityXi’anShanxi Province710032PR China

Secreted frizzled-related protein 5(SFRP5)plays a pivotal role in regulating the development of many tissues and organs,however,as an inhibitor of Wnt signaling,the role of SFRP5 in vitiligo remains ***,we speculated that SFRP5 might be associated with melanogenesis in melanocytes by regulating Wnt signaling in *** this study,we found that SFRP5 was overexpressed in the skin lesions of patients with *** with that in normal epidermal melanocytes(PIG1),the expression of SFRP5 was increased in vitiligo melanocytes(PIG3V).To investigate the effect of SFRP5 on melanin synthesis,PIG1 cells were infected with recombinant SFRP5 adenovirus(AdSFRP5),and PIG3V cells were infected with recombinant siSFRP5 adenovirus(AdsiSFRP5).The results showed that SFRP5 overexpression inhibited melanin synthesis in PIG1 cells through downregulation of microphthalmia-associated transcription factor(MITF)and its target proteins via suppression of the Wnt/b-catenin signaling ***,SFRP5 silencing increased melanin synthesis and activated the Wnt signaling pathway in PIG3V ***,SFRP5 overexpression also downregulated the transcriptional activity of T cell factor/lymphoid enhancer factor(TCF/LEF)in PIG1 ***,this inhibitory effect of SFRP5 on melanin synthesis was reversed by treatment with the b-catenin agonist,*** inhibitory action of SFRP5 in pigmentation was further confirmed in vivo using a nude mouse ***,our results indicate that SFRP5 can inhibit melanogenesis in ***,our findings showed that SFRP5 plays a vital role in the development of vitiligo,and thus may serve as a potential therapeutic target for vitiligo.

关键词： melanin synthesis Melanocytes MITF SFRP5 Vitiligo Wnt signaling

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Role of GTP-CHⅠ links PAH and TH in melanin synthesis in silkworm, Bombyx mori

Role of GTP-CHⅠ links PAH and TH in melanin synthesis in si...

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第十二届家（柞）蚕遗传育种暨良种繁育学术研讨会

作者：陈萍 Jiying Wang Haiyin Li Yan Li Peng Chen Tian Li Xi Chen Junjie Xiao Liang Zhang College of Biotechnology Southwest University

In insects, pigment patterns are formed by melanin, ommochromes, and pteridines. Here, the effects of pteridine synthesis on melanin formation were studied using 4th instar larvae of a wild-type silkworm strain（dazao） with normal color and markings. Results from injected larvae and in vitro integument culture indicated that decreased activity of guanosine triphosphate cyclohydrolase Ⅰ（GTP-CH Ⅰ, a rate-limiting enzyme for pteridine synthesis）, lowers BH4（6R-L-erythro-5,6,7,8-tetrahydrobiopterin, a production correlated with GTP-CH Ⅰ activity） levels and eliminates markings and coloration. The conversion of phenylalanine and tyrosine to melanin was prevented when GTP-CH Ⅰ was inhibited. When BH4 was added, phenylalanine was converted to tyrosine, and the tyrosine concentration increased. Tyrosine was then converted to melanin to create normal markings and coloration. Decreasing GTP-CH Ⅰ activity did not affect DOPA. GTP-CH Ⅰ affected melanin synthesis by generating the BH4 used in 2 key reaction steps:（1） conversion of phenylalanine to tyrosine by PAH（phenylalanine hydroxylase） and（2） conversion of tyrosine to DOPA by TH（tyrosine hydroxylase）. Expression profiles of BmGTPCH Ia, BmGTPCH Ib, BmTH, and BmPAH in the integument were consistent with the current findings.

关键词： silkworm guanosine triphosphate cyclohydrolase Ⅰ(GTP-CH Ⅰ) phenylalanine hydroxylase(PAH) tyrosine hydroxylase(TH) melanin synthesis

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Design, synthesis and Biological Activity of Novel Furocoumarin Derivatives as Stimulators of Melanogenesis and Tyrosinase in B16 Cells

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Chemical Research in Chinese Universities 2018年第3期34卷 408-414页

作者： NIU Chao ZANG Deng Haji Akber AISA Key Laboratory of Plant Resources and Chemistry in Arid Regions State Key Laboratory Basis of Xinjiang Indigenous Medicinal Plants Resource Utilization Xinjiang Technical Institute of Physics and Chemistry Chinese Academy of Sciences Urumqi 830011 P. R. China University of Chinese Academy of Sciences Beijing 100049 P. R. China

Sixteen novel and four known（4a, 4d, 4e, 4h） amine derivatives of furocoumarin were synthesized, then submitted to evaluation as stimulators of melanogenesis and tyrosinase in B16 murine cells. Among them, five compounds（4g, 4j-4m） showed potent activating effect on both melanogenesis and tyrosinase in vitro compared with positive control（8-MOP）, the most widely used drugs for vitiligo in clinic. Noticeably, compotmds 4h and 4j, which contain morpholine and piperazine, were recognized as the most effective stimnlator of melanogenesis and tyrosianse in B16 cells separately. These derivatives may serve as lead compounds for further drug discovery for the treatment of vitiligo.

关键词： Furocoumarin Amine melanin synthesis Tyrosinase Vitiligo

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Biomedical overview of *** molecular modeling,synthesis mechanism,and supramolecular properties regarding melanoma therapy

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BIOCELL 2022年第6期46卷 1391-1415页

作者： JUAN CARLOS STOCKERT ALFONSO BLÁZQUEZ-CASTRO Facultad de Medicina Instituto de Oncología“Angel H.Roffo”Universidad de Buenos AiresBuenos AiresC1417DTBArgentina Centro Integrativo de Biología y Química Aplicada(CIBQA) Universidad Bernardo O’HigginsSantiago8370854Chile Departamento de Biología Facultad de CienciasUniversidad Autónoma de MadridMadrid28049Spain

melanins represent one of the most ancient and important group of natural macromolecular *** have multiple biological roles in almost all organisms across the Phyla,examples being photoprotection,anti-oxidative action,radical scavenger activity,and heavy metal *** the biomedical point of view,melanocytes are involved in the origin of melanoma tumors,and the main therapeutic advances for their treatment have been revised in Part 1 of this *** chemical structure of eumelanin is a biological concern of great importance,and therefore,exploring theoretical molecular models and synthesis mechanisms will be here described,as well as molecular orbital features and supramolecular organization,which are responsible for the key properties that make these biological pigments so important,and so ***,this updated overview is devoted to describe present structural models and physico-chemical characteristics of eumelanin,in order to explain and utilize melanin properties on which new photothermal and ultrasonic protocols for melanoma treatment can be devised and applied.

关键词： Eumelanin melanin models melanin synthesis Molecular orbitals Supramolecular structure

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The main causes and corresponding solutions of skin pigmentation in the body

Journal of Dermatologic Science and Cosmetic Technology

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Journal of Dermatologic Science and Cosmetic Technology 2024年第2期1卷 38-44页

作者： Benyue Li Huaqian Mei Zhishan Zhou Jie Yang Yexiang Zhang Fengwei Qi Shandong Huawutang Biotechnology Co. LtdJinan 250101ShandongChina

The skin's normal color is primarily determined by the quantity and distribution of pigment,the level of hemoglobin in the skin's blood vessels,and various optical ***,mechanical damage from clothing renders certain areas of the body more susceptible to hyperpigmentation,such as the elbows and *** to research,various factors such as gender and weight have been found to influence skin *** mechanism of body skin pigmentation has been extensively studied with a particular focus on melanogenesis and related signaling ***,this article primarily focuses on elucidating the mechanisms governing body pigmentation while discussing strategies for managing skin whitening,encompassing influential factors and whitening methods.

关键词： Body whitening melanin synthesis Skin barrier Mechanical damage Cellular autophagy

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BmPAH catalyzes the first step in the melanin anabolism pathway in silkworm, Bombyx mori

BmPAH catalyzes the first step in the melanin anabolism path...

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第十二届家（柞）蚕遗传育种暨良种繁育学术研讨会

作者：陈萍 Li Li Jiying Wang Haiyin Li Yan Li Yin Lv 鲁成 College of Biotechnology Southwest University

Pigmentation during insect development is a primal adaptive requirement. In the silkworm, melanin is the primary component of larval pigments. The rate limiting substrate in melanin synthesis is tyrosine, which is converted from phenylalanine by the rate-limiting enzyme phenylalanine hydroxylase（PAH）. While the role of tyrosine, derived from phenylalanine, in the synthesis of fiber proteins has long been known, the role of PAH in melanin synthesis is still unknown in silkworm. To define the importance of PAH, we cloned the cDNA sequence of BmPAH and expressed its complete coding sequence using the Bac-to-Bac baculovirus expression system. Purified recombinant protein had high PAH activity, some tryptophan hydroxylase activity, but no tyrosine hydroxylase activity, which are typical properties of PAH in invertebrates. Because melanin synthesis is most robust during the embryonic stage and larval integument recoloring stage, we injected Bm PAH dsRNA into silkworm eggs and observed that decreasing BmPAH mRNA reduced neonatal larval tyrosine and caused insect coloration to fail. In vitro cultures and injection of 4th instar larval integuments with PAH inhibitor revealed that PAH activity was essential for larval marking coloration. These data show that Bm PAH is necessary for melanin synthesis and we propose that conversion of phenylalanine to tyrosine by PAH is the first step in the melanin biosynthetic pathway in the silkworm.

关键词： Bombyx mori melanin synthesis BmPAH pigmentation coloring

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