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Erythropoietin contributes to slow oxidative muscle fiber specification via PGC-1α and AMPK activation
Wang L.1; Jia Y.1; Rogers H.1; Suzuki N.2; Gassmann M.3; Wang Q.1; McPherron A.C.1; Kopp J.B.1; Yamamoto M.2; Noguchi C.T.1
2013-05-09
Source PublicationInternational Journal of Biochemistry and Cell Biology
ISSN13572725 18785875
Volume45Issue:7Pages:1155-1164
Abstract

Erythropoietin activity, required for erythropoiesis, is not restricted to the erythroid lineage. In light of reports on the metabolic effects of erythropoietin, we examined the effect of erythropoietin signaling on skeletal muscle fiber type development. Skeletal muscles that are rich in slow twitch fibers are associated with increased mitochondrial oxidative activity and corresponding expression of related genes compared to muscle rich in fast twitch fibers. Although erythropoietin receptor is expressed on muscle progenitor/precursor cells and is down regulated in mature muscle fibers, we found that skeletal muscles from mice with high erythropoietin production in vivo exhibit an increase in the proportion of slow twitch myofibers and increased mitochondrial activity. In comparison, skeletal muscle from wild type mice and mice with erythropoietin activity restricted to erythroid tissue have fewer slow twitch myofibers and reduced mitochondrial activity. PGC-1α activates mitochondrial oxidative metabolism and converts the fast myofibers to slow myofibers when overexpressed in skeletal muscle and PGC-1α was elevated by 2-fold in mice with high erythropoietin. In vitro erythropoietin treatment of primary skeletal myoblasts increased mitochondrial biogenesis gene expression including PGC-1α by 2.6-fold, CytC by 2-fold, oxygen consumption rate by 2-fold, and citrate synthase activity by 58%. Erythropoietin also increases AMPK, which induces PGC-1α and stimulates slow oxidative fiber formation. These data suggest that erythropoietin contributes to skeletal muscle fiber programming and metabolism, and increases PGC-1α and AMPK activity during muscle development directly to affect the proportion of slow/fast twitch myofibers in mature skeletal muscle. © 2013 Elsevier Ltd. All rights reserved.

KeywordAmpk Pgc-1α Erythropoietin Mitochondrial Activity Slow Twitch Fiber
DOI10.1016/j.biocel.2013.03.007
URLView the original
Indexed BySCI
WOS Research AreaBiochemistry & Molecular Biology ; Cell Biology
WOS SubjectBiochemistry & Molecular Biology ; Cell Biology
WOS IDWOS:000321229100001
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Cited Times [WOS]:17   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionFaculty of Health Sciences
Affiliation1.National Institute of Diabetes and Digestive and Kidney Diseases
2.Tohoku University School of Medicine
3.University of Zurich
Recommended Citation
GB/T 7714
Wang L.,Jia Y.,Rogers H.,et al. Erythropoietin contributes to slow oxidative muscle fiber specification via PGC-1α and AMPK activation[J]. International Journal of Biochemistry and Cell Biology,2013,45(7):1155-1164.
APA Wang L..,Jia Y..,Rogers H..,Suzuki N..,Gassmann M..,...&Noguchi C.T..(2013).Erythropoietin contributes to slow oxidative muscle fiber specification via PGC-1α and AMPK activation.International Journal of Biochemistry and Cell Biology,45(7),1155-1164.
MLA Wang L.,et al."Erythropoietin contributes to slow oxidative muscle fiber specification via PGC-1α and AMPK activation".International Journal of Biochemistry and Cell Biology 45.7(2013):1155-1164.
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