Abstract

Gravitational unloading, a model for microgravity and muscle disuse, induces a profound shift in the phenotype of postural muscles, such as the rat soleus, characterized by a transition from slow-twitch to fast-twitch fiber types. This adaptation is primarily mediated by the downregulation of the slow-twitch myosin heavy chain I(β) (MyHC I(β)) isoform, a key determinant of muscle function and fatigue resistance. This study investigates the time-dependent changes in the nuclear content of specific transcription factors implicated in the regulation of the MyHC I(β) gene expression in the rat soleus muscle following the onset of gravitational unloading. The objective was to elucidate the early molecular signaling events that precede the observed changes in MyHC I(β) mRNA and protein levels. Using biochemical and molecular techniques, including Western blotting and immunohistochemistry on isolated muscle nuclei, we tracked the time course of key regulatory factors. Our findings reveal a rapid and significant alteration in the nuclear localization of transcription factors, such as NFATc1 and MEF2, within the first 24-72 hours of unloading. This temporal pattern suggests that the transcriptional machinery is an immediate target of mechanical unloading, initiating the cascade that leads to the slow-to-fast fiber type transition. These results highlight the critical role of nuclear signaling in cellular adaptation to altered mechanical load and provide a foundation for developing targeted countermeasures against muscle atrophy and deconditioning.