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J Appl Physiol (March 3, 2005). doi:10.1152/japplphysiol.01172.2004
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Submitted on October 18, 2004
Accepted on March 1, 2005

Gene expression of myogenic factors and phenotype-specific markers in electrically stimulated muscle of paraplegics

Kristian Vissing1, Jesper L. Andersen1, Stephen D.R. Harridge2, Claudia Sandri3, Andreas Hartkopp4, Michael Kjaer5, and Peter Schjerling1*

1 Department of Molecular Muscle Biology, Copenhagen Muscle Research Center, Rigshopitalet, Copenhagen, Denmark
2 Department of Physiology, University College London, London, United Kingdom
3 Department of Biomedical Sciences, Consiglio Nazionalle delle Ricerche Centre of Muscle Biology and Physiopathology, University of Padua, Padua, Italy
4 Centre for Spinal Cord Injured, Neuroscience Centre, Rigshospitalet, Copenhagen, Denmark
5 Sports Medicine Research Unit, Bispebjerg Hospital, Copenhagen, Denmark

* To whom correspondence should be addressed. E-mail: viridis{at}biobase.dk.

The transcription factors myogenin and MyoD have been suggested to be involved in maintaining slow and fast muscle fiber phenotypes in rodents, respectively. Whether this is also the case in human muscle is unknown. To test this, four weeks of chronic low-frequency electrical stimulation training of the tibialis anterior muscle of paraplegic subjects was used to evoke a fast-to-slow transformation in muscle phenotype. It was hypothesized that this would result from an upregulation of myogenin and a downregulation of MyoD. The training evoked the expected mRNA increase for slow fiber-specific markers myosin heavy chain I (MHC I) and 3-hydroxyacyl-CoA dehydrogenase A (HADHA), whereas an mRNA decrease was seen for fast fiber-specific markers MHC IIX and glycerol phosphate dehydrogenase (GOPDH). Although the slow fiberspecific markers citrate synthase (CS) and muscle fatty acid binding protein (mFABP) did not display a significant increase in mRNA, they did tend to increase. As hypothesized, myogenin mRNA was upregulated. However, contrary to the hypothesis, MyoD mRNA also increased, although later than myogenin. The mRNA levels of the other myogenic regulatory factor family members, myogenic factor 5 (Myf5) and myogenic regulatory factor 4 (MRF4) and the myocyte enhancer factor (MEF) family members, MEF2A and MEF2C, did not change. The results indicate that myogenin is indeed involved in the regulation of the slow/oxidative phenotype in human skeletal muscle fibers, whereas MyoD appears to have a more complex regulatory function.




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