Aspirin increases mitochondrial fatty acid oxidation

Uppala, Radha; Dudiak, Brianne M.; Beck, Megan E.; Bharathi, Sivakama S.; Zhang, Yuxun; Stolz, Donna B.; Goetzman, Eric S.

doi:10.1016/j.bbrc.2016.11.066

Cited by 25 publications

(17 citation statements)

References 38 publications

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“…Many of these children were later found to suffer from FAODs, most prominently MCAD deficiency [46]. Our laboratory has recently reported that, at least in cultured cells, aspirin inhibits peroxisomal FAO while driving mitochondrial FAO [47]. Based on our findings we postulate that aspirin overwhelms the defective MCAD enzyme by enhancing long-chain FAO flux, while at the same time inhibiting the peroxisomal pathway which could otherwise act as a safety valve to prevent lipotoxicity.…”

Section: Advances In Understanding Pathophysiologysupporting

confidence: 51%

Advances in the Understanding and Treatment of Mitochondrial Fatty Acid Oxidation Disorders

Goetzman

2017

Curr Genet Med Rep

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Purpose of review This review focuses on advances made in the past three years with regards to understanding the mitochondrial fatty acid oxidation (FAO) pathway, the pathophysiological ramifications of genetic lesions in FAO enzymes, and emerging therapies for FAO disorders. Recent findings FAO has now been recognized to play a key energetic role in pulmonary surfactant synthesis, T-cell differentiation and memory, and the response of the proximal tubule to kidney injury. Patients with FAO disorders may face defects in these cellular systems as they age. Aspirin, statins, and nutritional supplements modulate the rate of FAO under normal conditions and could be risk factors for triggering symptoms in patients with FAO disorders. Patients have been identified with mutations in the ACAD9 and ECHS1 genes, which may represent new FAO disorders. New interventions for long-chain FAODs are in clinical trials. Finally, post-translational modifications that regulate fatty acid oxidation protein activities have been characterized that represent important new therapeutic targets. Summary Recent research has led to a deeper understanding of FAO. New therapeutic avenues are being pursued that may ultimately cause a paradigm shift for patient care.

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Section: Advances In Understanding Pathophysiologysupporting

confidence: 51%

Advances in the Understanding and Treatment of Mitochondrial Fatty Acid Oxidation Disorders

Goetzman

2017

Curr Genet Med Rep

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“…According to previous studies, aspirin can interfere with fatty acid metabolism by activating the enzyme in mitochondria, leading to the increase in usage of fatty acid and level of reactive oxygen species in animal cells. 35,36 Herein, we further investigated the mode of action of aspirin on fatty metabolism in the model organism budding yeast and the pathogen C. albicans.…”

Section: Discussionmentioning

confidence: 99%

Aspirin Causes Lipid Accumulation and Damage to Cell Membrane by Regulating DCI1/OLE1 in Saccharomyces cerevisiae

Zhu

Yan

et al. 2020

Microbial Drug Resistance

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Aspirin is one of the most commonly used nonsteroidal anti-inflammatory drugs. Various potential pharmacological effects of aspirin, such as anticancer, antibacterial activity, and prolonging life expectancy have been discovered. However, the mechanism of aspirin is not fully elucidated. Herein, the effects of aspirin on fatty acid metabolism in yeast cell model Saccharomyces cerevisiae were studied. The results showed that aspirin can induce lipid accumulation and reduce the unsaturated fat index in cells. The assessment of cell membrane integrity demonstrated that aspirin caused damage to the cell membrane. These effects of aspirin were attributed to the alterations of the expression of DCI1 and OLE1. Similarly, aspirin was able to cause lipid accumulation and damage to the cell membrane by interfering with the expression of OLE1 in Candida albicans. These findings are expected to improve current understanding of the mode of action of aspirin and provide a novel strategy for antifungal drug design.

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“…In addition to biguanides, other clinically used drugs, including chloramphenicol 43,44 , aspirin 45,46 , statins 18 , and local anesthetics 47 , also inhibit mitochondrial functions. Our results indicate that pre-exposure to mitochondrial inhibitors may increase the toxicity of propofol.…”

Section: Pharmacological Suppression Of Mitochondrial Etc Increased Pmentioning

confidence: 99%

Propofol induces a metabolic switch to glycolysis and cell death in a mitochondrial electron transport chain-dependent manner

Sumi

Okamoto

Tanaka

et al. 2017

Preprint

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The intravenous anesthetic propofol (2,6-diisopropylphenol) has been used for the induction and maintenance of anesthesia in operating rooms and for sedation in intensive care units. Although there is no widely accepted definition of propofol infusion syndrome (PRIS), PRIS is defined as the development of metabolic acidosis, rhabdomyolysis, hyperkalemia, hepatomegaly, renal failure, arrhythmia, and progressive cardiac failure. In vitro evidence suggests that PRIS is related to the impaired mitochondrial function. There are indications that preexisting mitochondrial disorders predispose to PRIS. However, the precise molecular mechanisms, including mitochondrial defects and a metabolic conversion by propofol, are largely unknown as yet. To elucidate the underlying cellular and molecular mechanisms of PRIS, we investigated the effects of propofol on the cellular metabolic mode and cell death. We demonstrated that clinically relevant concentrations of propofol, used within a clinically relevant exposure time, suppressed the mitochondrial function, caused the generation of reactive oxygen species, and induced a metabolic switch, from oxidative phosphorylation to glycolysis, by targeting complexes I and III of mitochondria. The data also indicated that a predisposition to mitochondrial dysfunction, caused by a genetic mutation or pharmacological suppression of the electron transport chain by biguanides such as metformin and phenformin, promoted the cell death and caspase activation induced by propofol.

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Aspirin increases mitochondrial fatty acid oxidation

Cited by 25 publications

References 38 publications

Advances in the Understanding and Treatment of Mitochondrial Fatty Acid Oxidation Disorders

Advances in the Understanding and Treatment of Mitochondrial Fatty Acid Oxidation Disorders

Aspirin Causes Lipid Accumulation and Damage to Cell Membrane by Regulating DCI1/OLE1 in Saccharomyces cerevisiae

Propofol induces a metabolic switch to glycolysis and cell death in a mitochondrial electron transport chain-dependent manner

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