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Response of the JAK-STAT pathway to mammalian hibernation in 13-lined ground squirrel striated muscle

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Abstract

Over the course of the torpor-arousal cycle, hibernators must make behavioral, physiological, and molecular rearrangements in order to keep a very low metabolic rate and retain organ viability. 13-lined ground squirrels (Ictidomys tridecemlineatus) remain immobile during hibernation, and although the mechanisms of skeletal muscle survival are largely unknown, studies have shown minimal muscle loss in hibernating organisms. Additionally, the ground squirrel heart undergoes cold-stress, reversible cardiac hypertrophy, and ischemia–reperfusion without experiencing fatal impairment. This study examines the role of the Janus kinase–signal transducer and activator of transcription (JAK-STAT) signaling pathway in the regulation of cell stress in cardiac and skeletal muscles, comparing euthermic and hibernating ground squirrels. Immunoblots showed a fivefold decrease in JAK3 expression during torpor in skeletal muscle, along with increases in STAT3 and 5 phosphorylation and suppressors of cytokine signaling-1 (SOCS1) protein levels. Immunoblots also showed coordinated increases in STAT1, 3 and 5 phosphorylation and STAT1 inhibitor protein expression in cardiac muscle during torpor. PCR analysis revealed that the activation of these pro-survival signaling cascades did not result in coordinate changes in downstream genes such as anti-apoptotic B-cell lymphoma-2 (Bcl-2) family gene expression. Overall, these results indicate activation of the JAK-STAT pathway in both cardiac and skeletal muscles, suggesting a response to cellular stress during hibernation.

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Acknowledgments

We thank Dr. J. M. Hallenbeck at the NIH for providing ground squirrel tissues, Bryan E. Luu for advice and assistance with polymerase chain reaction and Luminex® assay preparation, and Jan Storey for editorial review of this manuscript. This work was supported by a Discovery Grant (#6793) from the Natural Sciences and Engineering Research Council of Canada and a grant from the Heart and Stroke Foundation of Canada (#G-14-0005874). KBS holds the Canada Research Chair in Molecular Physiology, SNT holds a NSERC Postdoctoral Fellowship, and SML held an NSERC Undergraduate Student Research Award.

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  1. Shannon N. Tessier

    Present address: Department of Surgery & Center for Engineering in Medicine, Massachusetts General Hospital & Harvard Medical School, Building 114 16th Street, Charlestown, MA, 02129, USA

  2. Joann Tye

    Present address: New Beginnings Ob/Gyn, 193 Mountain Avenue, Springfield, NJ, 07081, USA

Authors and Affiliations

  1. Institute of Biochemistry & Department of Biology, Carleton University, 1125 Colonel By Drive, Ottawa, ON, K1S 5B6, Canada

    Samantha M. Logan, Shannon N. Tessier, Joann Tye & Kenneth B. Storey

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  1. Samantha M. Logan
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Correspondence to Kenneth B. Storey.

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Logan, S.M., Tessier, S.N., Tye, J. et al. Response of the JAK-STAT pathway to mammalian hibernation in 13-lined ground squirrel striated muscle. Mol Cell Biochem 414, 115–127 (2016). https://doi.org/10.1007/s11010-016-2665-6

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