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Votion 2013 Abstract MiP2013

From Bioblast
Votion DM, Mouithys-Mickalad A, Ceusters Justine D, Lemieux H, Tosi I, Franck T, Art T, Niesten A, Serteyn D (2013) The challenge of understanding myopathies in horses using permeabilized muscle cells. Mitochondr Physiol Network 18.08.

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Marie-Dominique Votion

MiP2013, Book of Abstracts Open Access

Votion DM, Mouithys-Mickalad A, Ceusters Justine D, Lemieux H, Tosi I, Franck T, Art T, Niesten A, Serteyn D (2013)

Event: MiPNet18.08_MiP2013

In horses, myopathic syndromes are common but most often their aetiology and pathogenesis are unknown. Recently, the cause of Type 1 polysaccharide storage myopathy (PSSM) and the one of atypical myopathy (AM) have been discovered. Type 1 PSSM is caused by a glycogen synthase (GYS1) mutation [1] and is characterized by exercise-induced muscle damage. The frequently fatal syndrome of AM results from the ingestion of the toxin hypoglycin A contained in seeds of some Acer species [2]. The metabolite of hypoglycin A inhibits several acyl-CoA dehydrogenases leading to a multiple acyl-CoA dehydrogenases deficiency (MADD) phenotype. The mitochondrial respiration has never been determined in myopathic horses despite the potential role of mitochondria in the pathogenesis of inherited and acquired equine myopathies.

High-resolution respirometry (HRR) and multiple substrate-uncoupler-inhibitor titration (SUIT) protocols were applied to study mitochondrial respiration in triceps brachii of horses suffering from PSSM (N = 5), exertional rhabdomyolysis (ER) from unknown origin (N = 3), and from AM (N = 15). Respirometric parameters of myopathic horses were compared to those of healthy controls with specific fitness level according to the one of the group investigated [3].

With the exception of one PSSM horse (i.e. Horse PSSM+ in Fig. 1), all myopathic horses showed a severe decrease in muscle respiratory capacity. Flux control ratios, FCR, and substrate control ratios, SCR, indicate an increase of CI-linked respiratory capacity as a common feature to PSSM and ER horses whereas AM was characterized by a greater contribution of CII respiration on maximal OXPHOS capacity. This study shows that the understanding equine myopathies with HRR necessitates substrates supply to selected segments of the ET-pathway and determination of maximal OXPHOS and ET capacities.


โ€ข O2k-Network Lab: BE Liege Votion DM, CA Edmonton Lemieux H


Labels: MiParea: Respiration, mt-Biogenesis;mt-density, Exercise physiology;nutrition;life style, Pharmacology;toxicology  Pathology: Myopathy 

Organism: Horse  Tissue;cell: Skeletal muscle  Preparation: Permeabilized tissue 


Coupling state: OXPHOS, ET  Pathway: F, N, S, NS, ROX  HRR: Oxygraph-2k 

MiP2013, Veterinary 

Affiliations and author contributions

1 - Equine Clinic, Faculty of Veterinary Medicine, University of Liege, Belgium; 2 - Center for Oxygen Research and Development (CORD), Institute of Chemistry, University of Liege, Belgium; 3 - Campus Saint-Jean, University of Alberta, Edmonton, Canada. - Email: [email protected]


Figure 1

Fig. 1: OXPHOS (P) and ET-pathway (E) capacity (Oxygen flux [pmol O2.s-1.mg-1 wet weight) with CI- (GMP: glutamate+malate), CI+II- (GMSP and GMSE: glutamate+malate+succinate), and CII-substrate (S(Rot)E: succinate+rotenone); N: number of horses (2 or 3 runs per horse); n = number of runs for this horse. See text for other abbreviations.


References

  1. McCue ME, Valberg SJ, Miller MB, Wade C, DiMauro S, Akman HO, Mickelson, JR (2008) Glycogen synthase (GYS1) mutation causes a novel skeletal muscle glycogenosis. Genomics 91: 458-466.
  2. Votion DM, Van Galen G, Sweetman L, Boemer F, de Tullio P, Dopagne C, Lefรจre L, Mouihys-Mickalad A, Patarin F, Rouxhet S, Van Loon G, Serteyn D, Sponseller BT, Valberg SJ (2013) The toxic metabolite causing equine atypical myopathy in europe has been identified. Submitted.
  3. Votion DM, Gnaiger E, Lemieux H, Mouithys-Mickalad A, Serteyn D (2012) Physical fitness and mitochondrial respiratory capacity in horse skeletal muscle. PLoS One 7: e34890.