Melatonin-mediated upregulation of GLUT1 blocks exit from pluripotency by increasing the uptake of oxidized vitamin C in mouse embryonic stem cells
Melatonin-mediated upregulation of GLUT1 blocks exit from pluripotency by increasing the uptake of oxidized vitamin C in mouse embryonic stem cells
复制标题
DOI：
10.1096/fj.201601085r
复制
发表时间：
2017-04-01
期刊：
影响因子：
4.8
通讯作者：
Zhang, Yong
中科院分区：
文献类型：
--
作者：
Wu, Haibo;Song, Chao;Zhang, Yong
褪黑素和维生素C是强有力的抗氧化剂，可提高诱导性多能干细胞（iPSCs）的重编程效率。然而，维生素C和褪黑素联合治疗对胚胎干细胞（ESC）分化的影响尚未被研究。在这项研究中，我们发现褪黑素与维生素C协同作用，使小鼠胚胎干细胞的多能性脱离。这种作用与脱氢抗坏血酸（维生素C的氧化形式）通过葡萄糖转运蛋白1（Glut 1）转运蛋白的增加的摄取有关，而葡萄糖转运蛋白1（Glut 1）转运蛋白又通过褪黑素治疗而上调。细胞信号通路分析和特异性抑制途径分析表明，褪黑素通过激活PI 3 K/AKT和MAPK/ERK信号通路，促进Glut 1的表达。本研究结果为褪黑素在ESCs和iPSCs研究中的应用以及进一步研究褪黑素与ESCs的组合对细胞重编程的影响提供了理论基础。吴，H.，宋角，澳-地张杰，赵，J，傅，B.毛，T. Zhang， Y.褪黑素介导的GLUT 1的上调通过增加小鼠胚胎干细胞对氧化维生素C的摄取来阻断多能性的退出《法国国家统计局公报》第31卷，第1731-1743页（2017年）。www.fasebj.org
Melatonin and vitamin C are powerful antioxidants that improve the reprogramming efficiency of induced pluripotent stemcells (iPSCs). However, the effects of the combined treatment of vitamin C andmelatonin on the differentiation of embryonic stem cells (ESCs) have not yet been examined. In this study, we showed that melatonin synergizes with vitamin C to derail exit from pluripotency of mouse ESCs. This effect is related to the increased uptake of dehydroascorbate, the oxidized form of vitamin C, through glucose transporter 1 (Glut1) transporter, which in turn, is upregulated by melatonin treatment. Analysis of the cell signaling pathway profiling systems andspecificpathwayinhibitionindicatedthatmelatoninenhancesGlut1 expressionby activating thePI3K/AKT andMAPK/ERK signaling pathways. Our findings provide a theoretical basis for application ofmelatonin in research on ESCs and iPSCs and for further investigation of the effect of combinatorial compounds on cell reprogramming.- Wu, H., Song, C., Zhang, J., Zhao, J., Fu, B., Mao, T., Zhang, Y. Melatonin-mediated upregulation of GLUT1 blocks exit frompluripotency by increasing the uptake of oxidized vitamin C in mouse embryonic stem cells. FASEB J. 31, 1731-1743 (2017). www.fasebj.org