Nishizuka Makoto, Hayashi Takahiro, Asano Mami, Osada Shigehiro, Imagawa Masayoshi
Department of Molecular Biology, Graduate School of Pharmaceutical Sciences, Nagoya City University, 3-1 Tanabe-dori, Mizuho-ku, Nagoya, Aichi 467-8603, Japan.
Int J Mol Sci. 2014 Dec 9;15(12):22743-56. doi: 10.3390/ijms151222743.
KCNK10, a member of tandem pore domain potassium channel family, gives rise to leak K+ currents. It plays important roles in stabilizing the negative resting membrane potential and in counterbalancing depolarization. We previously demonstrated that kcnk10 expression is quickly elevated during the early stage of adipogenesis of 3T3-L1 cells and that reduction of kcnk10 expression inhibits adipocyte differentiation. However, the molecular mechanism of KCNK10 in adipocyte differentiation remains unclear. Here we revealed that kcnk10 is induced by 3-isobutyl-1-methylxanthine, a cyclic nucleotide phosphodiesterase inhibitor and a potent inducer of adipogenesis, during the early stage of adipocyte differentiation. We also demonstrated that KCNK10 functions as a positive regulator of mitotic clonal expansion (MCE), a necessary process for terminal differentiation. The reduction of kcnk10 expression repressed the expression levels of CCAAT/enhancer-binding protein β (C/EBPβ) and C/EBPδ as well as the phosphorylation level of Akt during the early phase of adipogenesis. In addition, knockdown of kcnk10 expression suppressed insulin-induced Akt phosphorylation. These results indicate that KCNK10 contributes to the regulation of MCE through the control of C/EBPβ and C/EBPδ expression and insulin signaling.
KCNK10是双孔结构域钾通道家族的成员之一，可产生钾离子泄漏电流。它在稳定负性静息膜电位以及平衡去极化过程中发挥着重要作用。我们之前证实，在3T3-L1细胞脂肪生成的早期阶段，kcnk10的表达迅速升高，并且kcnk10表达的降低会抑制脂肪细胞分化。然而，KCNK10在脂肪细胞分化中的分子机制仍不清楚。在此我们发现，在脂肪细胞分化的早期阶段，kcnk10由3-异丁基-1-甲基黄嘌呤（一种环核苷酸磷酸二酯酶抑制剂和一种有效的脂肪生成诱导剂）诱导产生。我们还证明，KCNK10作为有丝分裂克隆扩增（MCE，终末分化的一个必要过程）的正向调节因子发挥作用。kcnk10表达的降低在脂肪生成的早期阶段抑制了CCAAT/增强子结合蛋白β（C/EBPβ）和C/EBPδ的表达水平以及Akt的磷酸化水平。此外，kcnk10表达的敲低抑制了胰岛素诱导的Akt磷酸化。这些结果表明，KCNK10通过控制C/EBPβ和C/EBPδ的表达以及胰岛素信号传导，参与了对MCE的调节。
