Cargando…
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
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 hematopoiesi...
Autores principales: | , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8534767/ https://www.ncbi.nlm.nih.gov/pubmed/34685682 http://dx.doi.org/10.3390/cells10102703 |
_version_ | 1784587623982956544 |
---|---|
author | Kaiser, Lars Quint, Isabel Csuk, René Jung, Manfred Deigner, Hans-Peter |
author_facet | Kaiser, Lars Quint, Isabel Csuk, René Jung, Manfred Deigner, Hans-Peter |
author_sort | Kaiser, Lars |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-8534767 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-85347672021-10-23 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 Kaiser, Lars Quint, Isabel Csuk, René Jung, Manfred Deigner, Hans-Peter Cells Article 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. MDPI 2021-10-09 /pmc/articles/PMC8534767/ /pubmed/34685682 http://dx.doi.org/10.3390/cells10102703 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Kaiser, Lars Quint, Isabel Csuk, René Jung, Manfred Deigner, Hans-Peter 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 |
title | 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 |
title_full | 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 |
title_fullStr | 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 |
title_full_unstemmed | 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 |
title_short | 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 |
title_sort | 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 |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8534767/ https://www.ncbi.nlm.nih.gov/pubmed/34685682 http://dx.doi.org/10.3390/cells10102703 |
work_keys_str_mv | AT kaiserlars lineageselectivedisturbanceofearlyhumanhematopoieticprogenitorcelldifferentiationbythecommonlyusedplasticizerdi2ethylhexylphthalateviareactiveoxygenspeciesfattyacidoxidationmakesthedifference AT quintisabel lineageselectivedisturbanceofearlyhumanhematopoieticprogenitorcelldifferentiationbythecommonlyusedplasticizerdi2ethylhexylphthalateviareactiveoxygenspeciesfattyacidoxidationmakesthedifference AT csukrene lineageselectivedisturbanceofearlyhumanhematopoieticprogenitorcelldifferentiationbythecommonlyusedplasticizerdi2ethylhexylphthalateviareactiveoxygenspeciesfattyacidoxidationmakesthedifference AT jungmanfred lineageselectivedisturbanceofearlyhumanhematopoieticprogenitorcelldifferentiationbythecommonlyusedplasticizerdi2ethylhexylphthalateviareactiveoxygenspeciesfattyacidoxidationmakesthedifference AT deignerhanspeter lineageselectivedisturbanceofearlyhumanhematopoieticprogenitorcelldifferentiationbythecommonlyusedplasticizerdi2ethylhexylphthalateviareactiveoxygenspeciesfattyacidoxidationmakesthedifference |