Calcineurin-Aα alpha activation enhances the structure and function of regenerating muscles after myotoxic injury

Stupka, Nicole, Schertzer, Jonathon D., Bassel-Duby, Rhonda, Olson, Eric N. and Lynch, Gordon S. 2007, Calcineurin-Aα alpha activation enhances the structure and function of regenerating muscles after myotoxic injury, American journal of physiology - regulatory, integrative and comparative physiology, vol. 293, no. 2, pp. R686-R694.

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Title Calcineurin-Aα alpha activation enhances the structure and function of regenerating muscles after myotoxic injury
Author(s) Stupka, Nicole
Schertzer, Jonathon D.
Bassel-Duby, Rhonda
Olson, Eric N.
Lynch, Gordon S.
Journal name American journal of physiology - regulatory, integrative and comparative physiology
Volume number 293
Issue number 2
Start page R686
End page R694
Publisher American Physiological Society
Place of publication [Bethesda, Md.]
Publication date 2007-08
ISSN 0363-6119
1522-1490
Keyword(s) myotoxic injury
skeletal muscle
muscle function
Summary Calcineurin signaling is essential for successful muscle regeneration. Although calcineurin inhibition compromises muscle repair, it is not known whether calcineurin activation can enhance muscle repair after injury. Tibialis anterior (TA) muscles from adult wild-type (WT) and transgenic mice overexpressing the constitutively active calcineurin-Aα transgene under the control of the mitochondrial creatine kinase promoter (MCK-CnAα*) were injected with the myotoxic snake venom Notexin to destroy all muscle fibers. The TA muscle of the contralateral limb served as the uninjured control. Muscle structure was assessed at 5 and 9 days postinjury, and muscle function was tested in situ at 9 days postinjury. Calcineurin stimulation enhanced muscle regeneration and altered levels of myoregulatory factors (MRFs). Recovery of myofiber size and force-producing capacity was hastened in injured muscles of MCK-CnAα* mice compared with control. Myogenin levels were greater 5 days postinjury and myocyte enhancer factor 2a (MEF2a) expression was greater 9 days postinjury in muscles of MCK-CnAα* mice compared with WT mice. Higher MEF2a expression in regenerating muscles of MCK-CnAα* mice 9 days postinjury may be related to an increase of slow fiber genes. Calcineurin activation in uninjured and injured TA muscles slowed muscle contractile properties, reduced fatigability, and enhanced force recovery after 4 min of intermittent maximal stimulation. Therefore, calcineurin activation can confer structural and functional benefits to regenerating skeletal muscles, which may be mediated in part by differential expression of MRFs.
Language eng
Field of Research 060110 Receptors and Membrane Biology
Socio Economic Objective 970106 Expanding Knowledge in the Biological Sciences
HERDC Research category C1.1 Refereed article in a scholarly journal
Copyright notice ©2007, American Physiological Society
Persistent URL http://hdl.handle.net/10536/DRO/DU:30019975

Document type: Journal Article
Collection: Institute for Technology Research and Innovation
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Created: Mon, 28 Sep 2009, 17:16:36 EST by Nicole Stupka

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