Fargesin inhibits melanin synthesis in murine malignant and immortalized melanocytes by regulating PKA/CREB and P38/MAPK signaling pathways
Fargesin inhibits melanin synthesis in murine malignant and immortalized melanocytes by regulating PKA/CREB and P38/MAPK signaling pathways
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DOI：
10.1016/j.jdermsci.2019.03.004
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发表时间：
2019-04-01
影响因子：
4.6
通讯作者：
Ye, Xiyun
中科院分区：
文献类型：
--
作者：
Fu, Ting;Chai, Bowen;Ye, Xiyun
背景资料：目的：探讨fargesin抑制黑色素生成的新功能及其分子机制。方法：用不同浓度的fargesin处理B16 F10小鼠黑色素瘤细胞、Melan-a细胞和人表皮黑色素细胞，观察不同浓度fargesin对黑色素生成的影响。分别在490 nm和405 nm处用光谱法检测细胞外和细胞内黑色素含量。采用RT-qPCR和Western blot检测黑素生成酶的表达及PKA/CREB和p38 MAPK通路组分的活性。结果：中等剂量的Fargesin对小鼠B16 F10黑色素瘤细胞、正常黑素细胞株和斑马鱼黑素生成均有抑制作用。小眼症相关转录因子（MITF）的表达，其下游的黑素生成酶和酪氨酸酶活性也强烈降低fargesin。此外，UVB和forskolin诱导的黑色素生成增加可被fargesin处理完全逆转。Fargesin还有效地抑制PKA/CREB和p38 MAPK的激活以及它们的相互作用，这反过来又是负责MITF和黑素生成enzymes.Conclusions的表达：这些结果表明，Fargesin可以作为一种抗黑素生成剂，至少部分，通过抑制PKA/CREB和p38/MAPK信号通路。因此，法格辛及其衍生物未来可能会用于预防色素沉着过度疾病。(C)2019由Elsevier B. V.代表日本皮肤病研究学会发布。
Background: Fargesin is commonly used in the treatment of allergic rhinitis, inflammation, sinusitis and headache.Objective: The aim of the study is to investigate a new function of fargesin against melanin production and its underlying molecular mechanism.Methods: B16F10 mouse melanoma cells, Melan-a and human epidermal melanocytes were treated with different concentrations of fargesin for the indicated time. The extracellular and cellular melanin content was detected by spectrometry at 490 nm and 405 nm, respectively. RT-qPCR and Western blot analysis were used to exam the expression of melanogenic enzymes and the activities of PKA/CREB and p38 MAPK pathway components. Zebra fish was used as an in vivo model for studying the function of fargesin in regulating melanogenesis.Results: Fargesin effectively inhibited melanin production at moderate dose in mouse B16F10 melanoma cells, normal melanocyte cell lines and zebrafish. The expression of microphthalmia-associated transcription factor (MITF), its downstream melanogenic enzymes and tyrosinase activity were also strongly reduced by fargesin. Moreover, the increase of melanin production induced by UVB and forskolin could be fully reversed by fargesin treatment. Fargesin also effectively inhibited the activation of PKA/CREB and p38 MAPK as well as their interactions, which in turn is responsible for the expression of MITF and melanogenic enzymes.Conclusions: These results show that fargesin can function as an anti-melanogenic agent, at least in part, by inhibiting PKA/CREB and p38/MAPK signaling pathways. Therefore, fargesin and its derivatives may potentially be used for preventing hyperpigmentation disorders in the future. (C) 2019 Published by Elsevier B.V. on behalf of Japanese Society for Investigative Dermatology.