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

2020 ◽  
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.

scholarly journals 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 ◽  
Vol 10 (10) ◽  
pp. 2703
Author(s):  
Lars Kaiser ◽  
Isabel Quint ◽  
René Csuk ◽  
Manfred Jung ◽  
Hans-Peter Deigner
Keyword(s):  
Reactive Oxygen Species ◽  
Fatty Acid ◽  
Fatty Acid Oxidation ◽  
Energy Production ◽  
Hematopoietic Cells ◽  
Reactive Oxygen ◽  
Health Concern ◽  
Acid Oxidation ◽  
Oxygen Species ◽  
Ethylhexyl Phthalate

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.

scholarly journals The impact of reactive oxygen species in the development of cardiometabolic disorders: a review

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Roland Akhigbe ◽  
Ayodeji Ajayi
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Nicotinamide Adenine Dinucleotide Phosphate ◽  
Reactive Oxygen ◽  
Acid Oxidation ◽  
Ros Generation ◽  
Metabolic Memory ◽  
Oxygen Species ◽  
Cardiometabolic Disorders ◽  
The Impact

AbstractOxidative stress, an alteration in the balance between reactive oxygen species (ROS) generation and antioxidant buffering capacity, has been implicated in the pathogenesis of cardiometabolic disorders (CMD). At physiological levels, ROS functions as signalling mediators, regulates various physiological functions such as the growth, proliferation, and migration endothelial cells (EC) and smooth muscle cells (SMC); formation and development of new blood vessels; EC and SMC regulated death; vascular tone; host defence; and genomic stability. However, at excessive levels, it causes a deviation in the redox state, mediates the development of CMD. Multiple mechanisms account for the rise in the production of free radicals in the heart. These include mitochondrial dysfunction and uncoupling, increased fatty acid oxidation, exaggerated activity of nicotinamide adenine dinucleotide phosphate oxidase (NOX), reduced antioxidant capacity, and cardiac metabolic memory. The purpose of this study is to discuss the link between oxidative stress and the aetiopathogenesis of CMD and highlight associated mechanisms. Oxidative stress plays a vital role in the development of obesity and dyslipidaemia, insulin resistance and diabetes, hypertension via various mechanisms associated with ROS-led inflammatory response and endothelial dysfunction.

scholarly journals Inhibition of Fatty Acid Oxidation Promotes Macrophage Control of Mycobacterium tuberculosis

mBio ◽  
2020 ◽  
Vol 11 (4) ◽  
Author(s):  
Pallavi Chandra ◽  
Li He ◽  
Matthew Zimmerman ◽  
Guozhe Yang ◽  
Stefan Köster ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Mycobacterium Tuberculosis ◽  
Fatty Acid ◽  
Nadph Oxidase ◽  
Reactive Oxygen ◽  
Metabolic Reprogramming ◽  
Acid Oxidation ◽  
Oxygen Species ◽  
Content Type ◽  
Mitochondrial Fatty Acid

ABSTRACT Macrophage activation involves metabolic reprogramming to support antimicrobial cellular functions. How these metabolic shifts influence the outcome of infection by intracellular pathogens remains incompletely understood. Mycobacterium tuberculosis (Mtb) modulates host metabolic pathways and utilizes host nutrients, including cholesterol and fatty acids, to survive within macrophages. We found that intracellular growth of Mtb depends on host fatty acid catabolism: when host fatty acid β-oxidation (FAO) was blocked chemically with trimetazidine, a compound in clinical use, or genetically by deletion of the mitochondrial fatty acid transporter carnitine palmitoyltransferase 2 (CPT2), Mtb failed to grow in macrophages, and its growth was attenuated in mice. Mechanistic studies support a model in which inhibition of FAO generates mitochondrial reactive oxygen species, which enhance macrophage NADPH oxidase and xenophagy activity to better control Mtb infection. Thus, FAO inhibition promotes key antimicrobial functions of macrophages and overcomes immune evasion mechanisms of Mtb. IMPORTANCE Mycobacterium tuberculosis (Mtb) is the leading infectious disease killer worldwide. We discovered that intracellular Mtb fails to grow in macrophages in which fatty acid β-oxidation (FAO) is blocked. Macrophages treated with FAO inhibitors rapidly generate a burst of mitochondria-derived reactive oxygen species, which promotes NADPH oxidase recruitment and autophagy to limit the growth of Mtb. Furthermore, we demonstrate the ability of trimetazidine to reduce pathogen burden in mice infected with Mtb. These studies will add to the knowledge of how host metabolism modulates Mtb infection outcomes.

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