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Votion 2018 MiP2018
Coupling states OXPHOS  +
Has abstract [[Image:MITOEAGLE-logo.jpg|left|100px|link
[[Image:MITOEAGLE-logo.jpg|left|100px|link=http://www.mitoglobal.org/index.php/MITOEAGLE|COST Action MitoEAGLE]] Equine atypical myopathy (AM) is an acute environmental intoxication resulting from hypoglycin A (HGA) ingestion. In Europe, seeds and seedlings of ''Acer pseudoplatanus'' (sycamore maple tree) are the primarily sources of this naturally-occurring toxin [1]. Out of Europe, ackee and lychee may also cause HGA poisoning in human [2,3]. Metabolism of ingested HGA produces methylenecyclopropylacetic acid (MCPA) which impairs fatty acid metabolism with subsequent increased use of glucose. As a consequence, human and laboratory animals suffer from an acute hypoglycaemic syndrome due to blockade of gluconeogenesis after depletion of hepatic glycogen stores. In contrast, intoxicated equids usually show hyperglycaemia and suffer from a severe rhabdomyolysis syndrome targeting muscle groups enriched in mitochondria, such as postural, respiratory, and cardiac muscles [4]. Although HGA poisoning has been extensively studied in regard to the inhibition of mitochondrial β-oxidation and the mechanism leading to hypoglycaemia, the impact on mitochondrial respiration has been overlooked. In a previous study, a severe decrease (up to 49%) in mitochondrial respiration was observed in muscle microbiopsies taken from horses suffering from AM with NADH-linked substrates and succinate used separately (N, S) or in cocktail (NS) to stimulate respiration [5]. Thus, mitochondrial toxicity of HGA and/ or MCPA is not solely associated to fatty acid metabolism disturbance. To better understand the functional mitochondrial defects associated with AM and identify potential treatments, an ''in vitro'' model is needed. Firstly, we have observed that addition of serum of AM-affected horses (which contains HGA, MCPA and a general increase in acylcarnitine species) on cultured equine myoblasts depresses NS-linked respiration. Secondly, we have showed that MCPA but not HGA decreases OXPHOS capacity of N, S and NS-pathways in a dose-dependent manner. Thirdly, we have included short, medium and long chain fatty acids as substrates and confirmed inhibition of fatty acid (F) pathway by MCPA but not HGA. Although these protocols do not reveal the MCPA action site(s), these respirometric studies may serve as a basis for evaluating the effectiveness of selected therapeutics assumed to be of value to prevent and/ or counteract the mitochondrial dysfunction associated to HGA poisoning.
l dysfunction associated to HGA poisoning.  +
Has editor [[Plangger M]]  + , [[Kandolf G]]  +
Has title [[Image:20091010 Dominique VOTION Reduite.jpg|left|90px|Dominique-Marie Votion]] Functional diagnosis of mitochondrial defects in equine atypical myopathy and targeted mitochondrial therapy: a preliminary study.  +
Instrument and method Oxygraph-2k  +
Mammal and model Horse  +
MiP area Respiration  + , Pharmacology;toxicology  +
Pathways F  + , N  + , S  + , NS  +
Preparation Intact cells  +
Tissue and cell Skeletal muscle  +
Was published by MiPNetLab BE Liege Votion DM + , CA Edmonton Lemieux H +
Was submitted in year 2018  +
Was submitted to event MiP2018/MitoEAGLE Jurmala LV +
Was written by Zhou Y + , Gonzalez-Medina S + , Gustin P + , Mouithys-Mickalad AA + , Piercy RJ + , Marcillaud-Pitel C + , Lemieux H + , Votion DM +
Categories Abstracts
Modification date
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07:44:57, 20 August 2018  +
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