Evaluation of Functional Erythropoietin Receptor Status in Skeletal Muscle In Vivo Acute and Prolonged Studies in Healthy Human Subjects 英文参考文献.docVIP

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Evaluation of Functional Erythropoietin Receptor Status in Skeletal Muscle In Vivo Acute and Prolonged Studies in Healthy Human Subjects 英文参考文献.doc

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Evaluation of Functional Erythropoietin Receptor Status in Skeletal Muscle In Vivo Acute and Prolonged Studies in Healthy Human Subjects 英文参考文献

EvaluationofFunctionalErythropoietinReceptorStatus inSkeletalMuscleInVivo:AcuteandProlongedStudies inHealthyHumanSubjects BrittChristensen1,2*,CarstenLundby3,NielsJessen2,4,ThomasS.Nielsen2,PoulF.Vestergaard1,2 ,Niels M?ller1,2,HenriettePilegaard7,SteenB.Pedersen1,JohnJ.Kopchick5,6,JensOttoL.J?rgensen1 1Department ofEndocrinologyand Internal Medicine,NBG/THG,AarhusUniversityHospital,Aarhus, Denmark, 2MedicalResearchLaboratories,University ofAarhus, Aarhus, Denmark, 3Center for Integrative Human Physiology (ZIHP), Institute of Physiology, University of Zu¨rich, Zu¨rich, Switzerland, 4Department of Clinical Pharmacology,AarhusUniversityHospital,Aarhus,Denmark,5EdisonBiotechnologyInstitute,DepartmentofBiomedicalSciences,OhioUniversity,Athens,Ohio,United States of America, 6Department of Biomedical Sciences, Ohio University, Athens, Ohio, United States of America, 7Centre of Inflammation and Metabolism and CopenhagenMuscleResearchCentre,AugustKroghBuilding,DepartmentofBiology,UniversityofCopenhagen,Copenhagen,Denmark Abstract Background: Erythropoietin receptors have been identified in human skeletal muscle tissue, but downstream signal transductionhasnotbeeninvestigated.Wethereforestudiedinvivoeffectsofsystemicerythropoietinexposureinhuman skeletalmuscle. Methodology/Principal Findings: The protocols involved 1) acute effects of a single bolus injection of erythropoietin followedbyconsecutivemusclebiopsiesfor1–10hours,and2)aseparatestudywithprolongedadministrationfor16days withbiopsiesobtainedbeforeandafter.Thepresenceoferythropoietinreceptorsinmuscletissueaswellasactivationof Eposignallingpathways(STAT5,MAPK,Akt,IKK)wereanalysedbywesternblotting.Changesinmuscleproteinprofilesafter prolongederythropoietintreatmentwereevaluatedby2Dgel-electrophoresisandmassspectrometry.Thepresenceofthe erythropoietinreceptorinskeletalmusclewasconfirmed,bytheM20butnottheC20antibody.However,nosignificant changesinphosphorylationoftheEpo-R,STAT5,MAPK,Akt,Lyn,IKK,andp70S6Kaftererythropo