Spatial and temporal expression of hypoxia-inducible factor-1α during myogenesis in vivo and in vitro.
We investigated the spatial and temporal expression patterns of hypoxia-inducible factor-1α (HIF-1α) during muscle regeneration and myogenesis in a C2C12 cell culture system. The expression of HIF-1α synchronized with that of myogenic regulatory genes during muscle regeneration at both the mRNA and protein levels. The HIF-1α protein was localized in the nuclei of newly formed regenerating myofibers in three different muscle injury models, including freezing, bupivacaine injection, and muscular dystrophy. In myogenic cell culture, the HIF-1α protein was localized in the nucleus and cytoplasm of the majority of myoblasts and myotubes. HIF-1α protein expression decreased concomitant with the increased expression of MyoD and myogenin proteins after the induction of myogenic differentiation. We investigated the adaptive response of myoblasts to hypoxia-like conditions induced by treatment of cobalt chloride. This treatment allowed HIF-1α to accumulate and translocate to the nucleus to activate transcription of its target genes, suggesting that myoblasts adapted to acute hypoxia-like conditions through enhancing an HIF-1-dependent pathway. Our results provide insight into the possible involvement of HIF-1α in myogenesis in vivo and in vitro.
Wagatsuma
Akira
A
Department of Life Sciences, Graduate School of Arts and Sciences, The University of Tokyo, 3-8-1 Komaba, Meguro-ku, Tokyo, Japan. wagatsuma1969@yahoo.co.jp
Kotake
Naoki
N
Yamada
Shigeru
S
D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics; D002460:Cell Line; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D003035:Cobalt / Q000494:pharmacology; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics* / Q000378:metabolism*; D007150:Immunohistochemistry; D051379:Mice; D024510:Muscle Development / Q000187:drug effects / Q000235:genetics*; D018485:Muscle Fibers, Skeletal / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D017570:MyoD Protein / Q000235:genetics / Q000378:metabolism; D018008:Myogenin / Q000235:genetics / Q000378:metabolism; D055550:Protein Stability / Q000187:drug effects; D021381:Protein Transport / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012038:Regeneration / Q000235:genetics; D013997:Time Factors
C497443:Hif1a protein, mouse; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D017570:MyoD Protein; D018008:Myogenin; D012333:RNA, Messenger; D003035:Cobalt; C018021:cobaltous chloride