Expression of four muscle regulatory factors in normal and denervated adult rat hindlimb muscle

Sherry Lynn Voytik, Purdue University

Abstract

Skeletal muscle represents a heterogeneous population of muscle fibers working together to achieve the primary function of contractility. The presence of these fibers which differ in metabolic, contractile, and protein isoform properties within the same muscle allows it to meet a wide range of functional and contractile requirements. In an attempt to understand the regulatory mechanisms underlying the differential expression of phenotypic properties among adult skeletal muscle fiber subtypes (e.g., slow-twitch versus fast-twitch), we examined the expression levels of four muscle regulatory factors, MyoD, myogenin, myf-5, and MRF4, in normal adult rat muscles which differed in metabolic potential and fiber type population. All four muscle regulatory factors were expressed at detectable levels in the muscles studied; however, different muscles expressed different proportions of the factors. Myogenin expression was positively correlated 267c properties associated with slow-twitch muscles (e.g., oxidative potential, slow fiber population, and transcript levels of slow troponin I). Alternatively, MyoD expression was negatively correlated with the slow muscle phenotype. We then induced phenotypic changes in two fast-twitch muscles via denervation and subseqently monitored the time course of changes in expression of the four muscle regulatory factors. Transcript levels of all four of the factors accumulated as early as 24 hours following denervation. Myogenin expression was the most responsive to denervation with transcript levels 150-225 fold higher than innervated contralateral muscles at 7 days following denervation. MyoD, myf-5, and MRF4 showed modest increases in transcript levels as much as 5-, 21-, and 12-fold higher than innervated contralateral muscles. The fact that myogenin and MyoD expression is correlated with properties associated with slow and fast muscle subtypes and that all four muscle regulatory factors are responsive to environmental cues such as denervation suggest that they continue to regulate gene expression in adult skeletal muscle. Further studies are necessary to verify the association of muscle regulatory factor activity with differential expression of slow versus fast muscle phenotype.

Degree

Ph.D.

Advisors

Badylak, Purdue University.

Subject Area

Biomedical research|Veterinary services|Molecular biology

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