Invited Review: Effects of different activity and inactivity paradigms on myosin heavy chain gene expression in striated muscle

Abstract

The goal of this mini-review is to summarize findings concerning the role that different models of muscular activity and inactivity play in altering gene expression of the myosin heavy chain (MHC) family of motor proteins in mammalian cardiac and skeletal muscle. This was done in the context of examining parallel findings concerning the role that thyroid hormone (T(3), 3,5,3'-triiodothyronine) plays in MHC expression. Findings show that both cardiac and skeletal muscles of experimental animals are initially undifferentiated at birth and then undergo a marked level of growth and differentiation in attaining the adult MHC phenotype in a T(3)/activity level-dependent fashion. Cardiac MHC expression in small mammals is highly sensitive to thyroid deficiency, diabetes, energy deprivation, and hypertension; each of these interventions induces upregulation of the beta-MHC isoform, which functions to economize circulatory function in the face of altered energy demand. In skeletal muscle, hyperthyroidism, as well as interventions that unload or reduce the weight-bearing activity of the muscle, causes slow to fast MHC conversions. Fast to slow conversions, however, are seen under hypothyroidism or when the muscles either become chronically overloaded or subjected to intermittent loading as occurs during resistance training and endurance exercise. The regulation of MHC gene expression by T(3) or mechanical stimuli appears to be strongly regulated by transcriptional events, based on recent findings on transgenic models and animals transfected with promoter-reporter constructs. However, the mechanisms by which T(3) and mechanical stimuli exert their control on transcriptional processes appear to be different. Additional findings show that individual skeletal muscle fibers have the genetic machinery to express simultaneously all of the adult MHCs, e.g., slow type I and fast IIa, IIx, and IIb, in unique combinations under certain experimental conditions. This degree of heterogeneity among the individual fibers would ensure a large functional diversity in performing complex movement patterns. Future studies must now focus on 1) the signaling pathways and the underlying mechanisms governing the transcriptional/translational machinery that control this marked degree of plasticity and 2) the morphological organization and functional implications of the muscle fiber's capacity to express such a diversity of motor proteins.

Age-related changes and nutritional regulation of myosin heavy-chain composition in longissimus dorsi of commercial pigs

“…In the late finishing stage, muscle-fibre types could be not be unchanged, which was consistent with the report that several types of MyHC isoforms coexist in a single muscle fibre and are converted to an appropriate phenotype under the corresponding conditions (Baldwin and Haddad, 2001). These findings would provide a possibility for the nutritional regulation of muscle-fibre types in the late finishing period in the subsequent experiments.…”

Regeneration of Reinnervated Rat Soleus Muscle Is Accompanied by Fiber Transition Toward a Faster Phenotype

“…In the present study, however, we performed a more detailed analysis of the slow, hybrid, and fast fibers at both immunohistochemical and mRNA levels, examining also the size (atrophy state) of the different fiber populations, because these data are necessary for judging the reinnervation level of fibers before the induction of regeneration. Our new results, namely the significantly high number of I/II hybrids, as well as the increase in the number of both MHCIIA-or MHCIIX-expressing fibers, accompanied by respective changes in their mRNA levels, suggest a gradual slow-to-fast fiber switch in reinnervated soleus, which is regulated predominantly at the mRNA level (Schiaffino and Reggiani 1996;Baldwin and Haddad 2001;Pandorf et al 2006).…”

Dynamics of Myosin Heavy Chain Gene Regulation in Slow Skeletal Muscle

“…Its size, metabolic makeup, and contractile properties can all be altered to optimize function (1). Variability in contractile properties is achieved mainly by diversification in the motor protein myosin heavy chain (MHC), 2 where different isoforms are encoded by distinct genes (1,2). Of this family of eight MHC genes, six are tandemly linked and span ϳ420 kb in the rat on chromosome 10, with embryonic MHC situated at the most 5Ј end, sequentially followed by IIa, IIx, IIb, neonatal, and extraocular MHC.…”

“…Alterations to these conditions can drive the expression profile toward either a faster or slower contractile phenotype (I 7 IIa 7 IIx 7 IIb) depending on both the starting reference MHC profile of the muscle fiber and the newly imposed condition (1). For example, disuse, inactivity, lack of muscle innervation, and hyperthyroidism result in a shift of the MHC profile from slow (type I/IIa) to fast (type IIx/IIb) MHC isoforms in slow muscle fibers (8 -10).…”