Erythropoietin Does Not Enhance Skeletal Muscle Protein Synthesis Following Exercise in Young and Older Adults.

Séverine Lamon,Douglas Paddon-Jones,Andrew Garnham,Emily Arentson-Lantz,Paul A Della Gatta,Frederico Gerlinger-Romero,Evelyn Zacharewicz,Aaron P Russell,Lobna Ghobrial

doi:10.3389/fphys.2016.00292

Séverine Lamon, Douglas Paddon-Jones + Show 7 more

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https://doi.org/10.3389/fphys.2016.00292

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Purpose: Erythropoietin (EPO) is a renal cytokine that is primarily involved in hematopoiesis while also playing a role in non-hematopoietic tissues expressing the EPO-receptor (EPOR). The EPOR is present in human skeletal muscle. In mouse skeletal muscle, EPO stimulation can activate the AKT serine/threonine kinase 1 (AKT) signaling pathway, the main positive regulator of muscle protein synthesis. We hypothesized that a single intravenous EPO injection combined with acute resistance exercise would have a synergistic effect on skeletal muscle protein synthesis via activation of the AKT pathway.Methods: Ten young (24.2 ± 0.9 years) and 10 older (66.6 ± 1.1 years) healthy subjects received a primed, constant infusion of [ring-13C6] L-phenylalanine and a single injection of 10,000 IU epoetin-beta or placebo in a double-blind randomized, cross-over design. 2 h after the injection, the subjects completed an acute bout of leg extension resistance exercise to stimulate skeletal muscle protein synthesis.Results: Significant interaction effects in the phosphorylation levels of the members of the AKT signaling pathway indicated a differential activation of protein synthesis signaling in older subjects when compared to young subjects. However, EPO offered no synergistic effect on vastus lateralis mixed muscle protein synthesis rate in young or older subjects.Conclusions: Despite its ability to activate the AKT pathway in skeletal muscle, an acute EPO injection had no additive or synergistic effect on the exercise-induced activation of muscle protein synthesis or muscle protein synthesis signaling pathways.

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Erythropoietin (EPO) is a glycoproteic hormone that is primarily synthetized in the peritubular fibroblast-like cells of the renal cortex (Maxwell et al, 1993, 1997)
In interleukin-3-dependent cell lines characterized by high levels of EPOR, EPO-induced JAK2 activation appears to regulate the phosphatidylinositol 3kinase (PI3)/AKT (AKT) pathway and the Ras/mitogen-activated kinase (MAPK) signaling pathway (Damen et al, 1993; Miura et al, 1994; Constantinescu et al, 1999; Fisher, 2003)
No main effect of exercise was detected in the protein levels of phospho-p70-S6K and phospho4E-BP1, an age x exercise interaction was apparent for both (p < 0.05; Figures 4B,C)

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Introduction

Erythropoietin (EPO) is a glycoproteic hormone that is primarily synthetized in the peritubular fibroblast-like cells of the renal cortex (Maxwell et al, 1993, 1997). As the EPO molecule binds to its receptor, it induces a conformational change that activates the EPOR (Miura et al, 1991; Dusanter-Fourt et al, 1992) via the phosphorylation of the JAK2 protein (Constantinescu et al, 1999; Remy et al, 1999). In interleukin-3-dependent cell lines characterized by high levels of EPOR, EPO-induced JAK2 activation appears to regulate the phosphatidylinositol 3kinase (PI3)/AKT (AKT) pathway and the Ras/mitogen-activated kinase (MAPK) signaling pathway (Damen et al, 1993; Miura et al, 1994; Constantinescu et al, 1999; Fisher, 2003). EPO can activate AKT in extra-hematopoietic tissues including cardiomyocytes (Tramontano et al, 2003), endothelial cells (Elayappan et al, 2009) as well as in the skeletal muscle of mouse overexpressing the EPO protein (Hojman et al, 2009)

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