Activation of the erythropoietin receptor in human skeletal muscle.
OBJECTIVE
Erythropoietin receptor (EPOR) expression in non-hematological tissues has been shown to be activated by locally produced and/or systemically delivered EPO. Improved oxygen homeostasis, a well-established consequence of EPOR activation, is very important for human skeletal muscle performance. In the present study we investigate whether human skeletal muscle fibers and satellite cells express EPOR and if it is activated by exercise.


METHODS
Ten healthy males performed 65 min of cycle exercise. Biopsies were obtained from the vastus lateralis muscle and femoral arterio-venous differences in EPO concentrations were estimated.


RESULTS
The EPOR protein was localized in areas corresponding to the sarcolemma and capillaries. Laser dissection identified EPOR mRNA expression in muscle fibers. Also, EPOR mRNA and protein were both detected in human skeletal muscle satellite cells. In the initial part of the exercise bout there was a release of EPO from the exercising leg to the circulation, possibly corresponding to an increased bioavailability of EPO. After exercise, EPOR mRNA and EPOR-associated JAK2 phosphorylation were increased.


CONCLUSIONS
Interaction with JAK2 is required for EPOR signaling and the increase found in phosphorylation is therefore closely linked to the activation of EPOR. The receptor activation by acute exercise suggests that signaling through EPOR is involved in exercise-induced skeletal muscle adaptation, thus extending the biological role of EPO into the skeletal muscle.
Rundqvist
Helene
H
Section of Molecular Exercise Physiology, Department of Physiology and Pharmacology, Karolinska Institutet, 171 77 Stockholm, Sweden. helene.rundqvist@ki.se
Rullman
Eric
E
Sundberg
Carl Johan
CJ
Fischer
Helene
H
Eisleitner
Katarina
K
Ståhlberg
Marcus
M
Sundblad
Patrik
P
Jansson
Eva
E
Gustafsson
Thomas
T
D000222:Adaptation, Physiological / Q000235:genetics / Q000502:physiology; D000293:Adolescent; D000328:Adult; D002478:Cells, Cultured; D004921:Erythropoietin / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D015444:Exercise / Q000502:physiology*; D006801:Humans; D008297:Male; D018482:Muscle, Skeletal / Q000378:metabolism*; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D017467:Receptors, Erythropoietin / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D032496:Satellite Cells, Skeletal Muscle / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D015533:Transcriptional Activation; D055815:Young Adult
D017467:Receptors, Erythropoietin; D004921:Erythropoietin; D011505:Protein-Tyrosine Kinases