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Active fatty acid oxidation defines the cellular response towards reactive oxygen species

Lars Kaiser, Isabel Quint, René Csuk, Manfred Jung, Hans-Peter Deigner
doi: https://doi.org/10.1101/2020.07.13.200022
Lars Kaiser
1Institute of Precision Medicine, Medical and Life Sciences Faculty, Furtwangen University, Jakob-Kienzle-Straße 17, D-78054 Villingen-Schwenningen, Germany
2Institute of Pharmaceutical Sciences, University of Freiburg, Albertstraße 25, D-79104 Freiburg i. Br., Germany
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Isabel Quint
1Institute of Precision Medicine, Medical and Life Sciences Faculty, Furtwangen University, Jakob-Kienzle-Straße 17, D-78054 Villingen-Schwenningen, Germany
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René Csuk
3Organic Chemistry, Martin-Luther-University Halle-Wittenberg, Kurt-Mothes-Str. 2, D-06120 Halle (Saale), Germany
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Manfred Jung
2Institute of Pharmaceutical Sciences, University of Freiburg, Albertstraße 25, D-79104 Freiburg i. Br., Germany
4CIBSS – Centre for Integrative Biological Signalling Studies, University of Freiburg
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Hans-Peter Deigner
1Institute of Precision Medicine, Medical and Life Sciences Faculty, Furtwangen University, Jakob-Kienzle-Straße 17, D-78054 Villingen-Schwenningen, Germany
5Fraunhofer Institute IZI, Leipzig, EXIM Department, Schillingallee 68, D-18057 Rostock, Germany
6Associated member of Tuebingen University, Faculty of Science, Auf der Morgenstelle 8, D-72076 Tübingen, Germany
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  • For correspondence: hans-peter.deigner@hs-furtwangen.de
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Abstract

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.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted September 29, 2020.
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Active fatty acid oxidation defines the cellular response towards reactive oxygen species
Lars Kaiser, Isabel Quint, René Csuk, Manfred Jung, Hans-Peter Deigner
bioRxiv 2020.07.13.200022; doi: https://doi.org/10.1101/2020.07.13.200022
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Active fatty acid oxidation defines the cellular response towards reactive oxygen species
Lars Kaiser, Isabel Quint, René Csuk, Manfred Jung, Hans-Peter Deigner
bioRxiv 2020.07.13.200022; doi: https://doi.org/10.1101/2020.07.13.200022

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