Erythropoietin Induces a Shift of Muscle Phenotype from Fast Glycolytic to Slow Oxidative

Abstract

Sedentary and trained rat groups were studied. Each of these groups was either erythropoietin or placebo treated. Erythropoietin treatment increased significantly all haematological parameters studied. Training per se failed to modify haematological parameters. In a second time, we studied the specific activity of several oxidative enzymes in three different muscles. In sedentary rats, erythropoietin treatment increased significantly the specific activities of cytochrome c oxidase and L-3-hydroxyacyl CoA dehydrogenase in the soleus and those of L-3-hydroxyacyl CoA dehydrogenase and phosphofructokinase in both locomotor muscles. Training increased the oxidative enzymes activities in all muscles studied. In trained rats, effects of erythropoietin and training on oxidative enzymes activities were additive. In all erythropoietin treated muscles, the expression of slow twitch myosin light chains and oxidative myosin heavy chains increased. A similar phenomenon took place in all trained groups for light chains and in placebo treated trained rats for heavy chains. In trained groups, the effects of the hormone and of training were additive. Our results suggest strongly that two different mechanisms are involved in the response of skeletal muscles to erythropoietin treatment and to endurance training and probably whole body endurance is affected by erythropoietin treatment by an increase of oxygenation of all tissues.

erythropoietin - skeletal muscles - oxidative phenotype - rat

References

• 1 Baldwin K M, Fitts R H, Booth F W, Winder W W, Holloszy J O. Depletion of muscle and liver glycogen during exercise. Protective effect of training.  Pflügers Arch. 1975;  354 203-212
• 2 Baldwin K M, Winder W W, Terjung R L, Holloszy J O. Glycolytic enzymes in different types of skeletal muscles: adaptation to exercise.  Am J Physiol. 1973;  225 962-966
• 3 Balsom P D, Ekblom B, Sjödin B. Enhanced oxygen availability during high intensity intermittent exercise decreases anaerobic metabolite concentrations in blood.  Acta Physiol Scand. 1994;  150 455-456
• 4 Berglund B, Ekblom B. Effect of recombinant erythropoietin treatment on blood pressure and some hematological parameters in healthy men.  J Internal Med. 1991;  229 125-130
• 5 Cooperstein S J, Lazarow A. A microspectrophotometric method for the determination of cytochrome c oxidase.  J Biol Chem. 1951;  189 665-670
• 6 Bottinelli R, Betto R, Schiaffino S, Reggiani C. Unloaded shortening velocity and myosin heavy chain and alkali light chain isoform composition in rat skeletal muscle fibres.  J Physiol (London). 1994;  478 341-349
• 7 Ekblom B, Berglund B. Effect of erythropoietin administration on maximal aerobic power.  Scan J Med Sci Sports. 1991;  1 88-93
• 8 Henriksson J. Effects of physical training on the metabolism of skeletal muscle.  Diabetes Care. 1992;  15 1701-1711
• 9 Henriksson J. Muscle fuel selection: effect of exercise and training.  Proc Nut Soc. 1995;  54 125-138
• 10 Hodgson D R, Rose R J, DiMauro J, Allen J R. Effects of a submaximal treadmill training programme on histochemical properties, enzyme activities and glycogen utilisation of skeletal muscle in the horse.  Pflügers Arch. 1985;  354 203-212
• 11 Holloszy J O, Coyle E F. Adaptations of skeletal muscle to endurance exercise and their metabolic consequenses.  J Appl Physiol. 1984;  56 831-838
• 12 Howald H, Pette D, Simoneau J A, Uber A, Hoppeler H, Cerretelli P. Effects of chronic hypoxia on muscle enzyme activities.  Int J Sports Med. 1990;  11 (Suppl) S10-S14
• 13 Laemmli U K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4 (A new electrophoresis technique).  Nature. 1970;  227 680-685
• 14 Lavoie C, Diguet A, Milot M, Gareau R. Erythropoietin (rHuEPO) doping: effects of exercise on anaerobic metabolism in rats.  Int J Sports Med. 1998;  19 281-286
• 15 Mansour T. Studies on heart phophofructokinase: purification inhibition and activation.  J Biol Chem. 1963;  238 2285-2292
• 16 Meierhenrich R, Jedicke H, Voigt A, Lange H. The effect of erythropoietin on lactate, pyruvate and excess lactate under physical exercise in dialysis patients.  Clin Nephrol. 1996;  45 90-96
• 17 Pette D, Staron R S. Cellular and molecular diversities of mammalian skeletal muscle fibers. Rev Physiol.  Biochem Pharmacol. 1990;  116 1-76
• 18 Ricci G, Masotti M, De Paoli Vitali E, Vedovato M, Zanotti G. Effects of exercise on haematological parameters, serum iron, serum ferritin, red cell 2, 3-diphosphoglycerate and creatine contents, and serum erythropoietin in long distance runners during basal training.  Acta Haematol. 1988;  80 95-98
• 19 Schiaffino S, Reggiani C. Molecular diversity of myofibrillar proteins: gene regulation and functional significance.  Physiol Rev. 1996;  76 371-423
• 20 Srere P A. The citrate synthase.  Meth Enzymol. 1969;  13 3-26
• 21 Talmadge R J, Roy R R. Electrophoretic separation of rat skeletal muscle myosin heavy chain isoformes.  J Appl Physiol. 1993;  75 2337-2340
• 22 Verbrugge D J, Goodnough L T. The effect of recombinant human erythropoietin treatment on the endurance performance of Sprague-Dawley rats.  Scand J Clin Lab Invest. 1994;  54 55-59
• 23 Wahrmann J P, Winand R, Rieu M. Plasticity of skeletal myosin in endurance trained rats (I). A quantitative study.  Eur J Appl Physiol. 2001;  84 367-372
• 24 Wahrmann J P, Fulla Y, Rieu M, Kahn A, Dinh X. Altered myosin isoform expressionin rat muscles induced by a changed thyroid state.  Acta Physiol Scand. 2002;  176 233-243