Melanogenic Effects of Maclurin Are Mediated through the Activation of cAMP/PKA/CREB and p38 MAPK/CREB Signaling Pathways
Melanogenic Effects of Maclurin Are Mediated through the Activation of cAMP/PKA/CREB and p38 MAPK/CREB Signaling Pathways
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DOI：
10.1155/2019/9827519
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发表时间：
2019-12-23
影响因子：
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通讯作者：
Lee, Jongsung
中科院分区：
文献类型：
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作者：
Hwang, Young Sun;Oh, Sae Woong;Lee, Jongsung
黑素生成是皮肤合成黑色素以保护皮肤免受紫外线照射和其他外部应激的生物学过程。黑素细胞的异常生物学与色素脱失性皮肤病如白癜风密切相关。在这项研究中，我们研究了maclurin对黑素生成和细胞保护的影响。Maclurin增强细胞酪氨酸酶活性以及细胞黑色素水平。我们发现maclurin治疗增加了小眼相关转录因子（MITF），酪氨酸酶相关蛋白-（TRP-）1，TRP-2和酪氨酸酶的表达。机制上，maclurin通过环磷酸腺苷（cAMP）反应元件结合（CREB）蛋白依赖性上调MITF促进黑素生成。CREB激活被发现是由p38丝裂原活化蛋白激酶（MAPK）或cAMP-蛋白激酶A（PKA）信号转导介导的。此外，maclurin诱导的CREB磷酸化是通过激活cAMP/PKA和p38 MAPK信号通路介导的。Maclurin诱导的p44/42 MAPK激活的抑制也有助于其黑素生成活性。此外，maclurin显示对H2O2处理和UVB照射的人黑素细胞的保护作用。这些发现表明maclurin的黑素生成作用依赖于增加的MITF基因表达，这是由p38 MAPK/CREB和cAMP/PKA/CREB信号传导的激活介导的。因此，我们的研究结果表明，maclurin可能是有用的保护剂对色素减退的皮肤疾病。
Melanogenesis is the biological process which the skin pigment melanin is synthesized to protect the skin against ultraviolet irradiation and other external stresses. Abnormal biology of melanocytes is closely associated with depigmented skin disorders such as vitiligo. In this study, we examined the effects of maclurin on melanogenesis and cytoprotection. Maclurin enhanced cellular tyrosinase activity as well as cellular melanin levels. We found that maclurin treatment increased the expression of microphthalmia-associated transcription factor (MITF), tyrosinase-related protein- (TRP-) 1, TRP-2, and tyrosinase. Mechanistically, maclurin promoted melanogenesis through cyclic adenosine monophosphate (cAMP) response element binding (CREB) protein-dependent upregulation of MITF. CREB activation was found to be mediated by p38 mitogen-activated protein kinase (MAPK) or cAMP-protein kinase A (PKA) signaling. In addition, maclurin-induced CREB phosphorylation was mediated through the activation of both the cAMP/PKA and the p38 MAPK signaling pathways. Maclurin-induced suppression of p44/42 MAPK activation also contributed to its melanogenic activity. Furthermore, maclurin showed protective effects against H2O2 treatment and UVB irradiation in human melanocytes. These findings indicate that the melanogenic effects of maclurin depend on increased MITF gene expression, which is mediated by the activation of both p38 MAPK/CREB and cAMP/PKA/CREB signaling. Our results thus suggest that maclurin could be useful as a protective agent against hypopigmented skin disorders.