NADPH Oxidase 4 Regulates Cardiomyocyte Differentiation via Redox Activation of c-Jun Protein and the cis-Regulation of GATA-4 Gene Transcription
NADPH Oxidase 4 Regulates Cardiomyocyte Differentiation via Redox Activation of c-Jun Protein and the cis-Regulation of GATA-4 Gene Transcription
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DOI：
10.1074/jbc.m112.439844
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发表时间：
2013-05-31
影响因子：
4.8
通讯作者：
Brewer, Alison C.
中科院分区：
文献类型：
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作者：
Murray, Thomas V. A.;Smyrnias, Ioannis;Brewer, Alison C.
NADPH氧化酶4 （Nox4）产生活性氧（ROS），可以部分通过氧化还原调节转录因子的活性来调节细胞表型和功能。我们在这里证明了Nox4在多能胚胎癌细胞中驱动心肌细胞分化的潜力，并且我们表明这涉及到c-Jun的氧化还原激活。这反过来又通过GATA-4启动子内定义的高度保守的顺式作用基序上调GATA-4表达，这是心脏型分化的最早标记之一。因此，这些数据提示了一种机制，即ROS在体内多能细胞中调节心肌细胞表型的关键组织限制性决定因子的初始转录，包括GATA-4。由Nox4介导的广泛表达的氧化还原调节转录因子（如c-Jun）的ros依赖性激活是这一过程的基础。
NADPH oxidase 4 (Nox4) generates reactive oxygen species (ROS) that can modulate cellular phenotype and function in part through the redox modulation of the activity of transcription factors. We demonstrate here the potential of Nox4 to drive cardiomyocyte differentiation in pluripotent embryonal carcinoma cells, and we show that this involves the redox activation of c-Jun. This in turn acts to up-regulate GATA-4 expression, one of the earliest markers of cardiotypic differentiation, through a defined and highly conserved cis-acting motif within the GATA-4 promoter. These data therefore suggest a mechanism whereby ROS act in pluripotential cells in vivo to regulate the initial transcription of critical tissue-restricted determinant(s) of the cardiomyocyte phenotype, including GATA-4. The ROS-dependent activation, mediated by Nox4, of widely expressed redox-regulated transcription factors, such as c-Jun, is fundamental to this process.