Transcriptional regulation of the myosin heavy chain IIB gene in inactive rat soleus

Abstract

The myosin heavy chain (MHC) isoform composition of skeletal muscle is dependent, in part, on the functional demands of the muscle. The rat soleus muscle primarily expresses the slowcontracting type I MHC; however, chronic inactivity increases expression of the faster-contracting type II MHC isoforms. The purpose of this study was to identify the type IIb MHC promoter region(s) that regulate de novo transcription during chronic inactivity of the soleus induced by spinal cord isolation (SI; complete mid-thoracic and high sacral spinal cord transections plus deafferentation). Seven days after SI, transcription of IIb MHC was evidenced by increases in IIb pre-mRNA and mRNA. The activity of an ≈2.2-kb IIb promoter-firefly luciferase reporter plasmid increased in SI soleus over control as compared to that of a promoterless plasmid. Deletion analyses indicated that the regions encompassing −2237 to −1431, −1048 to −461, and −192 to −161 basepairs (bp) each contributed to the increase in transcriptional activity. Moreover, deletions or mutations of AT-rich regions in the proximal −192 bp region abolished the increased promoter activity. These results provide important insights related to how proximal IIb MHC promoter elements regulate the increased expression of the IIb MHC gene in response to inactivity of a predominantly slow postural muscle as it undergoes a remodeling of its phenotype and functional characteristics.

Spinalization and locomotor training differentially affect muscarinic acetylcholine receptor type 2 abutting on α‐motoneurons innervating the ankle extensor and flexor muscles

“…; McCall et al . ). These changes are in line with a switch of M2R receptors increasing their synaptic versus extra‐synaptic distribution in spinal rats.…”

Exercise Dosing to Retain Resistance Training Adaptations in Young and Older Adults

“…The plasticity of myosin heavy chain isofonn expression in response to altered loading is a complex phenomenon with multiple levels of regulation (2). Recent work from the Baldwin laboratory has begun to reveal key promoter elements (29) and epigenetic tnechanisms (e.g., histone modifications) (31) that infiuence transcriptional activities of the MHC genes. In light of the present human findings, it would be of great value in future studies to detemiine the mechanisms responsible for MHC shift reversal even in the presence of myofiber size preservation during attempted maintenance training.…”

Approaching Gravity as a Continuum Using the Rat Partial Weight-Bearing Model

“…In humans and rats, the soleus, a postural muscle [ 75 , 76 ] is mostly comprised of fibers expressing the type 1 myosin heavy chain (MyHC1), which generally act as slow-twitch oxidative fibers providing endurance. During disuse and total mechanical unloading, soleus myofibers have been reported to switch from type 1 to type 2 (i.e., generally fast-twitch glycolytic) [ 77 , 78 , 79 , 80 ], comparatively more prone to fatigue [ 81 , 82 ]. We also see this modification in soleus composition of rats undergoing reduced mechanical loading for up to 28 days, with 40% of gravitational loading having ~6–7% shift in Type I fiber percentage (Supplementary Tables) [ 40 , 41 ].…”