Lineage-Selective Disturbance of Early Human Hematopoietic Progenitor Cell Differentiation by the Commonly Used Plasticizer Di-2-ethylhexyl Phthalate via Reactive Oxygen Species: Fatty Acid Oxidation Makes the Difference

Cells

René Csuk¹  Manfred Jung²  Lars Kaiser³  Hans-Peter Deigner³  Isabel Quint³ 

[1] Department of Organic Chemistry, Martin-Luther-University Halle-Wittenberg, Kurt-Mothes-Str. 2, 06120 Halle (Saale), Germany;Institute of Pharmaceutical Sciences, University of Freiburg, Albertstraße 25, 79104 Freiburg im Breisgau, Germany;Institute of Precision Medicine, Medical and Life Sciences Faculty, Furtwangen University, Jakob-Kienzle-Straße 17, 78054 Villingen-Schwenningen, Germany;

关键词: endocrine-disrupting compounds;    fatty acid oxidation;    reactive oxygen species;    ROS quenching;    hematopoietic stem and progenitor cells;    di-2-ethylhexyl phthalate;   

DOI  :  10.3390/cells10102703

来源: DOAJ

【 摘 要 】

Exposure to ubiquitous endocrine-disrupting chemicals (EDCs) is a major public health concern. We analyzed the physiological impact of the EDC, di-2-ethylhexyl phthalate (DEHP), and found that its metabolite, mono-2-ethylhexyl phthalate (MEHP), had significant adverse effects on myeloid hematopoiesis at environmentally relevant concentrations. An analysis of the underlying mechanism revealed that MEHP promotes increases in reactive oxygen species (ROS) by reducing the activity of superoxide dismutase in all lineages, possibly via its actions at the aryl hydrocarbon receptor. This leads to a metabolic shift away from glycolysis toward the pentose phosphate pathway and ultimately results in the death of hematopoietic cells that rely on glycolysis for energy production. By contrast, cells that utilize fatty acid oxidation for energy production are not susceptible to this outcome due to their capacity to uncouple ATP production. These responses were also detected in non-hematopoietic cells exposed to alternate inducers of ROS.

【 授权许可】

Unknown