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Expression of nuclear factor of activated T cells (NFAT) and downstream muscle-specific proteins in ground squirrel skeletal and heart muscle during hibernation
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  • 作者:Yichi Zhang ; Kenneth B. Storey
  • 关键词:Ictidomys tridecemlineatus ; Hibernation ; Muscle remodelling ; Nuclear factor of activated T cells ; Western blots ; DPI–ELISA
  • 刊名:Molecular and Cellular Biochemistry
  • 出版年:2016
  • 出版时间:January 2016
  • 年:2016
  • 卷:412
  • 期:1-2
  • 页码:27-40
  • 全文大小:1,059 KB
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  • 作者单位:Yichi Zhang (1)
    Kenneth B. Storey (1)

    1. Department of Biology, Institute of Biochemistry, Carleton University, 1125 Colonel By Drive, Ottawa, ON, K1S 5B6, Canada
  • 刊物类别:Biomedical and Life Sciences
  • 刊物主题:Life Sciences
    Biochemistry
    Medical Biochemistry
    Oncology
    Cardiology
  • 出版者:Springer Netherlands
  • ISSN:1573-4919
文摘
The thirteen-lined ground squirrel (Ictidomys tridecemlineatus) undergoes remarkable adaptive changes during hibernation. Interestingly, skeletal muscle remodelling occurs during the torpor-arousal cycle of hibernation to prevent net muscle loss despite inactivity. Reversible cardiomyocyte hypertrophy occurs in cardiac muscle, allowing the heart to preserve cardiac output during hibernation, while avoiding chronic maladaptive hypertrophy post-hibernation. We propose that calcium signalling proteins [calcineurin (Cn), calmodulin (CaM), and calpain], the nuclear factor of activated T cell (NFAT) family of transcription factors, and the NFAT targets myoferlin and myomaker contribute significantly to adaptations taking place in skeletal and cardiac muscle during hibernation. Protein-level analyses were performed over several conditions: euthermic room temperature (ER), euthermic cold room (EC), entrance into (EN), early (ET), and late torpor (LT) time points, in addition to early (EA), interbout (IA), and late arousal (LA) time points using immunoblotting and DNA–protein interaction (DPI) enzyme-linked immunosorbent assay (ELISAs). In skeletal and cardiac muscle, NFATc2 protein levels were elevated during torpor. NFATc4 increased throughout the torpor-arousal cycle in both tissues, and NFATc1 showed this trend in cardiac muscle only. NFATc3 showed an elevation in DNA-binding activity but not expression during torpor. Myoferlin protein levels dramatically increased during torpor in both skeletal and cardiac muscle. Myomaker levels also increased significantly in cardiac muscle during torpor. Cardiac Cn levels remained stable, whereas CaM and calpain decreased throughout the torpor-arousal cycle. Activation and/or upregulation of NFATc2, c3, myoferlin, and myomaker at torpor could be part of a stress-response mechanism to preserve skeletal muscle mass, whereas CaM and calpain appear to initiate the rapid reversal of cardiac hypertrophy during arousal through downregulation of the NFAT–Cn pathway. Keywords Ictidomys tridecemlineatus Hibernation Muscle remodelling Nuclear factor of activated T cells Western blots DPI–ELISA

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