Proceedings of The Physiological Society

University of Oxford (2011) Proc Physiol Soc 23, C106

Oral Communications

Chronic Epo deficit induces exercise performance decrease and massive muscle proteolysis in running mouse

L. Mille-Hamard1, V. Billat1, E. Henry1, B. Bonnamy1, F. Joly3, P. Benech3, E. Barrey2

1. UBIAE U902 INSERM, University of Evry Val d'Essonne, Evry, France. 2. INRA, UMR1313 G


The protective role of Erythropoïetin (Epo) on tissue is still under debate. Indeed, it was reported in brain, kidney, heart but not in skeletal muscles. Meanwhile deficit or supplementation of Epo is known to modify the exercise performance and specially aerobic metabolism. Therefore, the purpose of this study was to investigate the protective effect of Epo in muscle and to examine the relationship between this potential protective effect and aerobic metabolism improvement. The performance of 17 mice (9 Epo-deficient (Epo-d) and 8 inbred control) was determined by running on a treadmill with oxygen uptake ( ) measurement. Mice were sacrified 24h after a last exhaustive treadmill exercise at the critical speed (CS). The Tibialis anterior and soleus muscles were removed. Total RNA was extracted from the muscles for gene expression analysis by microarray and quantitative real time PCR validation (RT-qPCR). The hematocrit (Htc) of the Epo-d mice was reduced by 50% compared with the control group (p<0.05). Also their performance was reduced by 25 to 30 % depending on the variables: vPeak, (p < 0.01), CS (p < 0.01), and max (p < 0.001). Moreover, vPeak and max of all mice and within each group were correlated with the Htc. A total of 1583 genes exhibited significant changes of expression levels (p < 0.05) between the Epo-d and the control mice. This set contained 68 up-regulated genes (normalized ratio > 1.4), 115 down-regulated genes (normalized ratio < 0.80). Most of the significant genes were moderately modulated genes (0.80 < normalized ratio < 1.4 ). According to data mining analysis, the exercise in Epo-d mice induced muscular proteolysis, hypoxia and oxydative stress which may be explained by glycolysis and mitochondrial phospho-oxidation inhibition, lowered cytoskeleton components and defective intra cellular transport. These results suggest that Epo have a protective role on skeletal muscles.

Where applicable, experiments conform with Society ethical requirements