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Spatial and temporal expression of hypoxia-inducible factor-1α during myogenesis in vivo and in vitro

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Abstract

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.

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Acknowledgments

This study was supported in part by Grant-in Aid for Scientific Research (C) from the Japan Society for the promotion of Science (Grant no. 22500658 to A.W.).

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Authors and Affiliations

  1. Department of Life Sciences, Graduate School of Arts and Sciences, The University of Tokyo, 3-8-1 Komaba, Meguro-ku, Tokyo, Japan

    Akira Wagatsuma & Shigeru Yamada

  2. Department of Advanced Interdisciplinary Studies (AIS), Graduate School of Engineering, The University of Tokyo, 4-6-1 Komaba, Meguro-ku, Tokyo, Japan

    Naoki Kotake

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  1. Akira Wagatsuma
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Correspondence to Akira Wagatsuma.

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Wagatsuma, A., Kotake, N. & Yamada, S. Spatial and temporal expression of hypoxia-inducible factor-1α during myogenesis in vivo and in vitro. Mol Cell Biochem 347, 145–155 (2011). https://doi.org/10.1007/s11010-010-0622-3

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