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Article

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

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Institute of Precision Medicine, Medical and Life Sciences Faculty, Furtwangen University, Jakob-Kienzle-Straße 17, 78054 Villingen-Schwenningen, Germany
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Institute of Pharmaceutical Sciences, University of Freiburg, Albertstraße 25, 79104 Freiburg im Breisgau, Germany
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Department of Organic Chemistry, Martin-Luther-University Halle-Wittenberg, Kurt-Mothes-Str. 2, 06120 Halle (Saale), Germany
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CIBSS—Centre for Integrative Biological Signalling Studies, University of Freiburg, 79104 Freiburg im Breisgau, Germany
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Fraunhofer Institute IZI, Leipzig, EXIM Department, Schillingallee 68, 18057 Rostock, Germany
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Associated Member of Faculty of Science, Tuebingen University, Auf der Morgenstelle 8, 72076 Tübingen, Germany
*
Author to whom correspondence should be addressed.
Academic Editors: Edward E. Schmidt, Hozumi Motohashi and Anna Kipp
Cells 2021, 10(10), 2703; https://doi.org/10.3390/cells10102703
Received: 9 September 2021 / Revised: 1 October 2021 / Accepted: 5 October 2021 / Published: 9 October 2021
(This article belongs to the Topic Cellular Redox Homeostasis)
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. View Full-Text
Keywords: endocrine-disrupting compounds; fatty acid oxidation; reactive oxygen species; ROS quenching; hematopoietic stem and progenitor cells; di-2-ethylhexyl phthalate; mono-2-ethylhexyl phthalate; hematopoiesis; hematotoxicity endocrine-disrupting compounds; fatty acid oxidation; reactive oxygen species; ROS quenching; hematopoietic stem and progenitor cells; di-2-ethylhexyl phthalate; mono-2-ethylhexyl phthalate; hematopoiesis; hematotoxicity
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MDPI and ACS Style

Kaiser, L.; Quint, I.; Csuk, R.; Jung, M.; Deigner, H.-P. 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 2021, 10, 2703. https://doi.org/10.3390/cells10102703

AMA Style

Kaiser L, Quint I, Csuk R, Jung M, Deigner H-P. 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. 2021; 10(10):2703. https://doi.org/10.3390/cells10102703

Chicago/Turabian Style

Kaiser, Lars, Isabel Quint, René Csuk, Manfred Jung, and Hans-Peter Deigner. 2021. "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 10, no. 10: 2703. https://doi.org/10.3390/cells10102703

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