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This Article Full Text Full Text (PDF) All Versions of this Article: 297/3/C556    most recent 00046.2009v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by LaFramboise, W. A. Articles by Wiseman, R. W. PubMed PubMed Citation Articles by LaFramboise, W. A. Articles by Wiseman, R. W.

MUSCLE CELL BIOLOGY AND CELL MOTILITY

Acute molecular response of mouse hindlimb muscles to chronic stimulation

¹Department of Pathology and University of Pittsburgh Cancer Institute, University of Pittsburgh School of Medicine, Shadyside Hospital, Pittsburgh; and ²Department of Pediatrics, Drexel University School of Medicine, Allegheny General Hospital, Pittsburgh, Pennsylvania; ³School of Health Sciences, Exercise Science Division, Central Michigan University, Mount Pleasant; and Biomedical Imaging Research Center, Departments of ⁴Physiology and ⁵Radiology, Michigan State University, East Lansing, Michigan

Submitted 23 January 2009 ; accepted in final form 15 July 2009

Stimulation of the mouse hindlimb via the sciatic nerve was performed for a 4-h period to investigate acute muscle gene activation in a model of muscle phenotype conversion. Initial force production (1.6 ± 0.1 g/g body wt) declined 45% within 10 min and was maintained for the remainder of the experiment. Force returned to initial levels upon study completion. An immediate-early growth response was present in the extensor digitorum longus (EDL) muscle (FOS, JUN, activating transcription factor 3, and musculoaponeurotic fibrosarcoma oncogene) with a similar but attenuated pattern in the soleus muscle. Transcript profiles showed decreased fast fiber-specific mRNA (myosin heavy chains 2A and 2B, fast troponins T₃ and I, -tropomyosin, muscle creatine kinase, and parvalbumin) and increased slow transcripts (myosin heavy chain-1β/slow, troponin C slow, and tropomyosin 3y) in the EDL versus soleus muscles. Histological analysis of the EDL revealed glycogen depletion without inflammatory cell infiltration in stimulated versus control muscles, whereas ultrastructural analysis showed no evidence of myofiber damage after stimulation. Multiple fiber type-specific transcription factors (tea domain family member 1, nuclear factor of activated T cells 1, peroxisome proliferator-activated receptor- coactivator-1 and -β, circadian locomotor output cycles kaput, and hypoxia-inducible factor-1) increased in the EDL along with transcription factors characteristic of embryogenesis (Kruppel-like factor 4; SRY box containing 17; transcription factor 15; PBX/knotted 1 homeobox 1; and embryonic lethal, abnormal vision). No established in vivo satellite cell markers or genes activated in our parallel experiments of satellite cell proliferation in vitro (cyclins A₂, B₂, C, and E₁ and MyoD) were differentially increased in the stimulated muscles. These results indicated that the molecular onset of fast to slow phenotype conversion occurred in the EDL within 4 h of stimulation without injury or satellite cell recruitment. This conversion was associated with the expression of phenotype-specific transcription factors from resident fiber myonuclei, including the activation of nascent developmental transcriptional programs.

myofiber; myocyte; fiber type; satellite cell; expression profiling; transcription factor; plasticity; myogenesis; contraction; force; chronic stimulation; histology