TNFα-signal and cAMP-mediated signals oppositely regulate melanoma- associated ganglioside GD3 synthase gene in human melanocytes.
TNFα-signal and cAMP-mediated signals oppositely regulate melanoma- associated ganglioside GD3 synthase gene in human melanocytes.
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TNFα信号和cAMP介导的信号相反地调节人黑素细胞中与黑素瘤相关的神经节苷脂GD3合酶基因。
DOI：
10.1038/s41598-019-51333-3
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发表时间：
2019
期刊：
影响因子：
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通讯作者：
Furukawa K.
中科院分区：
文献类型：
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作者：
Takeuchi R;Kambe M;Miyata M;Jeyadevan U;Tajima O;Furukawa K;Furukawa K.
分析神经节苷脂代谢酶在黑素细胞中的表达和调控对了解神经节苷脂在黑素瘤发生中的作用具有重要意义。在这项研究中，我们分析了正常黑素细胞中负责神经节苷脂合成的糖基转移酶基因的表达和调控机制。我们曾报道UVB照射角质形成细胞培养上清可诱导黑素细胞神经节苷脂GD 3合成酶基因表达上调，主要是TNFα所致，然后我们发现去除培养上清中的二丁酰环AMP和IBMX也可导致GD 3合成酶基因表达上调。向培养基中添加增加cAMP的α-黑素细胞刺激激素导致GD 3合酶基因表达水平显著降低，PKA抑制剂增强GD 3合酶基因水平。这些结果表明，通过TNFα和cAMP介导的信号相反地调节黑素细胞中GD 3合酶基因的表达。IKK抑制剂的结果表明，TNFα可能通过NF-κB信号传导诱导黑素细胞中GD 3合酶基因表达。当黑色素瘤细胞处理这些因素，没有波动的GD 3合酶基因的表达水平观察到，虽然IKK抑制剂显着抑制它，表明神经节苷脂合酶基因的调节在黑色素细胞和黑色素瘤之间的不同方式。
Analyses of expression and regulation of ganglioside synthases in melanocytes are important to understand roles of gangliosides in melanomagenesis. In this study, we analyzed the expression and regulatory mechanisms of glycosyltransferase genes responsible for ganglioside synthesis in normal melanocytes. We reported previously that culture supernatants of UVB-irradiated keratinocytes induced upregulation of ganglioside GD3 synthase gene in melanocytes, and mainly TNFα was responsible for it. Then, we found that elimination of dibutyryl cyclic AMP and IBMX from the medium also resulted in upregulation of the GD3 synthase gene. The addition of α-melanocyte-stimulating hormone which increases cAMP, to the medium led to a significant reduction in the GD3 synthase gene expression level, and a PKA inhibitor enhanced the GD3 synthase gene level. These results suggest that signals mediated via TNFα and cAMP oppositely regulate GD3 synthase gene expression in melanocytes. The results of an IKK inhibitor indicate the possibility that TNFα induces GD3 synthase gene expression via NF-κB signaling in melanocytes. When melanoma cells were treated by these factors, no fluctuation in the GD3 synthase gene expression level was observed, although an IKK inhibitor significantly suppressed it, suggesting that ganglioside synthase genes are regulated in distinct manners between melanocytes and melanomas.