Endocrine disrupting compounds (EDC) are ubiquitous in the human environment, displaying a highly relevant research topic. The impact of EDC on the differentiation of primitive cells, e.g. in hematopoiesis, is of particular interest. We found profound inhibitory effects of di-2-ethylhexyl phthalate (DEHP) on erythropoiesis and dendropoiesis, mediated via reactive oxygen species (ROS) generation. Neutrophil differentiation, however, was not affected by DEHP. ROS leads to a shift from glycolysis to the pentose phosphate pathway and diminishes ATP generation from glycolysis, ultimately resulting in apoptosis in both cell types. In neutrophils, ATP generation is held constant by active fatty acid oxidation (FAO), rendering these cells highly resistant against ROS. This relationship also holds true in HUVEC and HepG2 cells, also in combination with other organic peroxides. We, therefore, uncover a key mechanism for ROS quenching which further explains the distinct ROS quenching ability of different tissues.

中文翻译：

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活性脂肪酸氧化定义了细胞对活性氧的反应

内分泌干​​扰化合物（EDC）在人类环境中无处不在，显示出高度相关的研究主题。EDC对原始细胞分化的影响，例如在造血中，特别令人关注。我们发现邻苯二甲酸二-2-乙基己基酯（DEHP）对红细胞生成和树突细胞生成具有深远的抑制作用，这是通过活性氧（ROS）的产生介导的。然而，中性粒细胞的分化不受DEHP的影响。ROS导致从糖酵解途径转变为磷酸戊糖途径，并减少了糖酵解过程中ATP的产生，最终导致两种细胞类型的凋亡。在中性粒细胞中，ATP通过活性脂肪酸氧化（FAO）保持恒定，从而使这些细胞对ROS具有高度抵抗力。这种关系在HUVEC和HepG2细胞中也适用，还可以与其他有机过氧化物结合使用。因此，我们发现了ROS淬灭的关键机制，进一步解释了不同组织的ROS淬灭能力。