Modulation of Pax3 and Pax7 protein expression and localization in inactive skeletal muscle

Abstract

We previously have reported that myogenic regulatory factor (MRF; MyoD and myogenin) proteins are upregulated in skeletal muscles of denervated (Den) and, to a lesser extent, spinal cord isolated (SI) rats (Hyatt et al. AJP, 2003). The majority of these MRFs in both models of muscle inactivity were localized in fiber myonuclei rather than satellite cells. The purpose of this study was to determine whether paired box proteins (Pax3 and Pax7), which are thought to regulate the expression of MRFs, are similarly expressed and localized in the medial gastrocnemius muscle after 1, 8, or 28 days of Den or SI. Relative to the control group, muscle mass was 34 and 25% lower in the Den and SI groups at 8 days. At 28 days, atrophy had plateaued in the SI (27%) but not Den (66%) rats. Pax3 and Pax7 proteins were minimally expressed at 1 and 8 days in control, Den, and SI rats. At 28 days, Pax3 and Pax7 were 90- and 55-fold and 24- and 8-fold higher in Den and SI than control rats, respectively. Furthermore, Pax3 and Pax7 expression was ~4- and 8-fold higher in Den than SI muscles. Immunohistochemistry showed Pax3 and Pax7 localized in nuclei outside the muscle fibers, presumably in satellite cells or adult stem cells, and not in myonuclei. Combined with our previous observations, these results identify a Pax3/Pax7-independent mechanism for MRF expression in post-mitotic, fully differentiated adult muscle fibers. Supported, in part, by NIH NS16333.