Inhibition of fatty acid oxidation by etomoxir impairs NADPH production and increases reactive oxygen species resulting in ATP depletion and cell death in human glioblastoma cells

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.

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Evaluation of fatty acid oxidation by reactive oxygen species induced in liquids using atmospheric-pressure nonthermal plasma jets

Journal of Physics D Applied Physics ◽

10.1088/0022-3727/48/42/424010 ◽

2015 ◽

Vol 48 (42) ◽

pp. 424010 ◽

Cited By ~ 4

Author(s):

Atsushi Tani ◽

Satoshi Fukui ◽

Satoshi Ikawa ◽

Katsuhisa Kitano

Keyword(s):

Reactive Oxygen Species ◽

Fatty Acid ◽

Fatty Acid Oxidation ◽

Atmospheric Pressure ◽

Reactive Oxygen ◽

Nonthermal Plasma ◽

Plasma Jets ◽

Acid Oxidation ◽

Oxygen Species

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10E,12Z-conjugated linoleic acid impairs adipocyte triglyceride storage by enhancing fatty acid oxidation, lipolysis, and mitochondrial reactive oxygen species

The Journal of Lipid Research ◽

10.1194/jlr.m035188 ◽

2013 ◽

Vol 54 (11) ◽

pp. 2964-2978 ◽

Cited By ~ 28

Author(s):

Laura J. den Hartigh ◽

Chang Yeop Han ◽

Shari Wang ◽

Mohamed Omer ◽

Alan Chait

Keyword(s):

Reactive Oxygen Species ◽

Fatty Acid ◽

Linoleic Acid ◽

Conjugated Linoleic Acid ◽

Fatty Acid Oxidation ◽

Reactive Oxygen ◽

Acid Oxidation ◽

Oxygen Species ◽

Mitochondrial Reactive Oxygen Species

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

10.1101/2020.07.13.200022 ◽

2020 ◽

Cited By ~ 1

Author(s):

Lars Kaiser ◽

Isabel Quint ◽

René Csuk ◽

Manfred Jung ◽

Hans-Peter Deigner

Keyword(s):

Reactive Oxygen Species ◽

Fatty Acid ◽

Fatty Acid Oxidation ◽

Cellular Response ◽

Reactive Oxygen ◽

Endocrine Disrupting Compounds ◽

Acid Oxidation ◽

Oxygen Species ◽

Atp Generation ◽

The Impact

AbstractEndocrine 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.

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