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.
Highlights
Melanin, synthesized in vertebrates by a specific type of cell called melanocytes, is the main component of human hair, eyes, and skin color
Abnormalities of melanin synthesis, metabolism, and melanocytes function in human can lead to related skin diseases, such as albinism, vitiligo caused by insufficient pigment synthesis or loss of pigment, freckles, senile plaques, and even melanoma caused by abnormal accumulation of pigment
Neural crest cells specialized by transcription factor SOX10 have the potential to differentiate into melanoblasts, the pigment precursor cells [5]
Summary
Melanin, synthesized in vertebrates by a specific type of cell called melanocytes, is the main component of human hair, eyes, and skin color. Abnormalities of melanin synthesis, metabolism, and melanocytes function in human can lead to related skin diseases, such as albinism, vitiligo caused by insufficient pigment synthesis or loss of pigment, freckles, senile plaques, and even melanoma caused by abnormal accumulation of pigment. The key transcription factor MITF (microphthalmia-associated transcription factor) expressed in melanocytes precursor cells can activate the expression of other melanocytes differentiation and migration related proteins, such as TYR (tyrosinase), DCT (dopachrome tautomerase, known as tyrosinase-related protein 2), and TRP1 (tyrosinase-related protein 1) [6]. Following the expression of MITF, TYR, DCT, and TRP1, melanoblasts gradually differentiate into melanocytes. After the formation of melanocytes, melanin synthesis is regulated by melanogenic enzymes which contain three major proteins: tyrosinase and tyrosinase-related proteins 1 and 2 [7]
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