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Biomolecules ; 10(9)2020 09 19.
Article in English | MEDLINE | ID: mdl-32961761

ABSTRACT

It has been reported that 5-hydroxytryptamine (5-HT) is related to melanogenesis in mice and melanoma cells. However, the underlying mechanisms of 5-HT in regulating pigmentation remains unknown. In this study, we aim to clarify the regulatory mechanism of 5-HT in the pigmentation of zebrafish embryos and B16F10 cells. Our results show that 5-HT induces the pigmentation of zebrafish embryos in a dosage-dependent manner at concentrations of 0.01-1 mM. Whole mount in situ hybridizations and qRT-PCR in zebrafish embryos indicate that the expression of neural crest cells marker gene sox10 is not changed in embryos treated with 5-HT compared to control group. The expression of mitfa, the marker gene of melanoblasts, is increased in the presence of 5-HT. Furthermore, 5-HT increased the expression of regeneration associated genes, namely kita, mitfa, and dct, after ablation of the melanogenic cells in zebrafish embryos. The experiments in B16F10 cells show that 5-HT promotes melanin synthesis by up-regulating the expression of key proteins MITF, TYR, TRP-1, and TRP-2. Especially, the small molecule inhibitor of PKA signaling, but not AKT and MAPK signaling, attenuates the up-regulation of MITF and TYR resulted from 5-HT induction in B16F10 cells. These results will help us to further understand the regulatory network of vertebrate pigmentation.


Subject(s)
Melanins/biosynthesis , Melanocytes/drug effects , Pigmentation/drug effects , Serotonin/pharmacology , Stem Cells/drug effects , Zebrafish/genetics , Animals , Cell Line, Tumor , Dose-Response Relationship, Drug , Embryo, Nonmammalian/cytology , Embryo, Nonmammalian/drug effects , Embryo, Nonmammalian/metabolism , Gene Expression Regulation, Developmental/drug effects , Larva/drug effects , Larva/metabolism , Larva/physiology , Melanocytes/cytology , Melanocytes/metabolism , Microphthalmia-Associated Transcription Factor/genetics , Microphthalmia-Associated Transcription Factor/metabolism , Neural Crest/cytology , Neural Crest/drug effects , Neural Crest/metabolism , Pigmentation/genetics , Regeneration/drug effects , Regeneration/genetics , Stem Cells/cytology , Stem Cells/metabolism , Zebrafish/embryology , Zebrafish/metabolism , Zebrafish Proteins/genetics , Zebrafish Proteins/metabolism
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