Barrey E.,CNRS Unit of Integrative Biology of Adaptation to Exercise |
Barrey E.,French National Institute for Agricultural Research |
Jayr L.,CNRS Unit of Integrative Biology of Adaptation to Exercise |
Mucher E.,CNRS Unit of Integrative Biology of Adaptation to Exercise |
And 9 more authors.
Animal Genetics | Year: 2012
Recurrent exertional rhabdomyolysis (RER) is frequently observed in race horses like trotters. Some predisposing genetic factors have been described in epidemiological studies. However, the exact aetiology is still unknown. A calcium homeostasis disruption was suspected in previous experimental studies, and we suggested that a transcriptome analysis of RER muscles would be a possible way to investigate the pathway disorder. The purpose of this study was to compare the gene expression profile of RER vs. control muscles in the French Trotter to determine any metabolic or structural disruption. Total RNA was extracted from the gluteal medius and longissimus lumborum muscles after biopsies in 15 French Trotter horses, including 10 controls and 5 RER horses affected by 'tying-up' with high plasmatic muscular enzyme activities. Gene expression analysis was performed on the muscle biopsies using a 25K oligonucleotide microarray, which consisted of 24 009 mouse and 384 horse probes. Transcriptome analysis revealed 191 genes significantly modulated in RER vs. control muscles (P < 0.05). Many genes involved in fatty acid oxidation (CD36/FAT, SLC25A17), the Krebs cycle (SLC25A11, SLC25A12, MDH2) and the mitochondrial respiratory chain were severely down-regulated (tRNA, MT-ND5, MT-ND6, MT-COX1). According to the down-regulation of RYR1, SLC8A1 and UCP2 and up-regulation of APP and HSPA5, the muscle fibre calcium homeostasis seemed to be greatly affected by an increased cytosolic calcium and a depletion of the sarcoplasmic reticulum calcium. Gene expression analysis suggested an alteration of ATP synthesis, with severe mitochondrial dysfunction that could explain the disruption of cytosolic calcium homeostasis and inhibition of muscular relaxation. © 2011 The Authors, Animal Genetics © 2011 Stichting International Foundation for Animal Genetics.
Mille-Hamard L.,CNRS Unit of Integrative Biology of Adaptation to Exercise |
Billat V.L.,CNRS Unit of Integrative Biology of Adaptation to Exercise |
Henry E.,CNRS Unit of Integrative Biology of Adaptation to Exercise |
Bonnamy B.,CNRS Unit of Integrative Biology of Adaptation to Exercise |
And 4 more authors.
BMC Medical Genomics | Year: 2012
Background: Erythropoietin (EPO) is known to improve exercise performance by increasing oxygen blood transport and thus inducing a higher maximum oxygen uptake (VO2max). Furthermore, treatment with (or overexpression of) EPO induces protective effects in several tissues, including the myocardium. However, it is not known whether EPO exerts this protective effect when present at physiological levels. Given that EPO receptors have been identified in skeletal muscle, we hypothesized that EPO may have a direct, protective effect on this tissue. Thus, the objectives of the present study were to confirm a decrease in exercise performance and highlight muscle transcriptome alterations in a murine EPO functional knock-out model (the EPO-d mouse). Methods. We determined VO2max peak velocity and critical speed in exhaustive runs in 17 mice (9 EPO-d animals and 8 inbred controls), using treadmill enclosed in a metabolic chamber. Mice were sacrificed 24h after a last exhaustive treadmill exercise at critical speed. The tibialis anterior and soleus muscles were removed and total RNA was extracted for microarray gene expression analysis. Results: The EPO-d mices hematocrit was about 50% lower than that of controls (p<0.05) and their performance level was about 25% lower (p<0.001). A total of 1583 genes exhibited significant changes in their expression levels. However, 68 genes were strongly up-regulated (normalized ratio>1.4) and 115 were strongly down-regulated (normalized ratio<0.80). The transcriptome data mining analysis showed that the exercise in the EPO-d mice induced muscle hypoxia, oxidative stress and proteolysis associated with energy pathway disruptions in glycolysis and mitochondrial oxidative phosphorylation. Conclusions: Our results showed that the lack of functional EPO induced a decrease in the aerobic exercise capacity. This decrease was correlated with the hematocrit and reflecting poor oxygen supply to the muscles. The observed alterations in the muscle transcriptome suggest that physiological concentrations of EPO exert both direct and indirect muscle-protecting effects during exercise. However, the signaling pathway involved in these protective effects remains to be described in detail. © 2012 Mille-Hamard et al.; licensee BioMed Central Ltd.