Myosin heavy chain isoform expression following reduced neuromuscular activity: Potential regulatory mechanisms

Talmadge, Robert J.

doi:10.1002/(sici)1097-4598(200005)23:5<661::aid-mus3>3.0.co;2-j

Cited by 251 publications

(237 citation statements)

References 156 publications

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“…However, no direct molecular link between the PCr/ATP ratio and the control of gene transcription has been clearly identified to date. Present knowledge of the molecular mechanisms of myosin and enzymatic protein expression suggests that a prolonged increase in cytosolic calcium concentration explains the preferential transcription of genes associated with the slow oxidative muscle phenotype (32,33). In resting muscles, UCP1 activity results in a decrease in the mitochondrial ⌬ Hϩ and cytosolic phosphorylation potentials.…”

Section: Discussionmentioning

confidence: 99%

High Level of Uncoupling Protein 1 Expression in Muscle of Transgenic Mice Selectively Affects Muscles at Rest and Decreases Their IIb Fiber Content

Couplan

Gelly

Goubern³

et al. 2002

Journal of Biological Chemistry

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The mitochondrial uncoupling protein of brown adipose tissue (UCP1) was expressed in skeletal muscle and heart of transgenic mice at levels comparable with the amount found in brown adipose tissue mitochondria. These transgenic mice have a lower body weight, and when related to body weight, food intake and energy expenditure are increased. A specific reduction of muscle mass was observed but varied according to the contractile activity of muscles. Heart and soleus muscle are unaffected, indicating that muscles undergoing regular contractions, and therefore with a continuous mitochondrial ATP production, are protected. In contrast, the gastrocnemius and plantaris muscles showed a severely reduced mass and a fast to slow shift in fiber types promoting mainly IIa and IIx fibers at the expense of fastest and glycolytic type IIb fibers. These observations are interpreted as a consequence of the strong potential dependence of the UCP1 protonophoric activity, which ensures a negligible proton leak at the membrane potential observed when mitochondrial ATP production is intense. Therefore UCP1 is not deleterious for an intense mitochondrial ATP production and this explains the tolerance of the heart to a high expression level of UCP1. In muscles at rest, where ATP production is low, the rise in membrane potential enhances UCP1 activity. The proton return through UCP1 mimics the effect of a sustained ATP production, permanently lowering mitochondrial membrane potential. This very likely constitutes the origin of the signal leading to the transition in fiber types at rest. Uncoupling protein 1 (UCP1)1 is expressed exclusively in brown adipose tissue (reviewed in Refs. 1 and 2). Its presence in brown fat mitochondria is responsible for heat production by the mitochondria in brown adipocytes. UCP1 allows return of protons into the matrix without ATP synthesis, and therefore dissipates the proton electrochemical gradient built up after proton pumping by the respiratory complexes. When this gradient reaches high values this makes proton pumping and thus substrate oxidation less easy and therefore slows down respiration. Activity of UCP1 prevents this rise of the proton gradient and therefore allows respiration to occur at a high rate, without phosphorylation of ADP into ATP, and therefore energy is instantaneously released as heat. The essential role of the UCP1 in thermogenesis is illustrated by the cold intolerance of mice whose ucp1 gene has been disrupted (3). Recently, two genes coding for proteins highly homologous to UCP1 have been described (reviewed in Refs. 4 -6). Although there are experimental evidence supporting the hypothesis of an uncoupling activity of these proteins (7,8), their physiological relevance is still incompletely resolved (9 -11). We intended to obtain transgenic mice overexpressing the UCP1 in skeletal muscles, with the aim of examining the effects of the presence of this uncoupling protein on the pattern of myosin expression and metabolic characteristics of locomotor muscles. Two other reports pub...

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Section: Discussionmentioning

confidence: 99%

High Level of Uncoupling Protein 1 Expression in Muscle of Transgenic Mice Selectively Affects Muscles at Rest and Decreases Their IIb Fiber Content

Couplan

Gelly

Goubern³

et al. 2002

Journal of Biological Chemistry

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“…In human muscle there are three types of MHC-MHC-I, MHC-IIa, MHC-IIx (IIb). 42 The type of MHC expressed in human skeletal muscle determines the characteristics of the muscle. The histochemical staining properties of a muscle fiber, and its fiber type classification, are closely associated to the MHC that is expressed.…”

Section: Histochemistry and Myosin Heavy Chain Analysis Of Human Paramentioning

confidence: 99%

“…The histochemical staining properties of a muscle fiber, and its fiber type classification, are closely associated to the MHC that is expressed. 42 Generally, muscle fibers in humans do not express more than one discrete MHC type. However, when muscle is transforming from chronic disuse after spinal cord injury, the number of hybrid fibers coexpressing two MHC types increases dramatically.…”

Section: Histochemistry and Myosin Heavy Chain Analysis Of Human Paramentioning

confidence: 99%

Muscular, Skeletal, and Neural Adaptations Following Spinal Cord Injury

Shields¹

2002

J Orthop Sports Phys Ther

136

106

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Spinal cord injury is associated with adaptations to the muscular, skeletal, and spinal systems. Experimental data are lacking regarding the extent to which rehabilitative methods may influence these adaptations. An understanding of the plasticity of the muscular, skeletal, and spinal systems after paralysis may be important as new rehabilitative technologies emerge in the 21st century. Moreover, individuals injured today may become poor candidates for future scientific advancements (cure) if their neuromusculoskeletal systems are irreversibly impaired. The primary purpose of this paper is to explore the physiological properties of skeletal muscle as a result of spinal cord injury; secondarily, to consider associated changes at the skeletal and spinal levels.Muscular adaptations include a transformation to faster myosin, increased contractile speeds, shift to the right on the torque-frequency curve, increased fatigue, and enhanced doublet potentiation. These muscular adaptations may be prevented in individuals with acute paralysis and partially reversed in individuals with chronic paralysis. Moreover, the muscular changes may be coordinated with motor unit and spinal circuitry adaptations. Concurrently, skeletal adaptations, as measured by bone mineral density, show extensive loss within the first six months after paralysis. The underlying science governing neuromusculoskeletal adaptations after paralysis will help guide professionals as new rehabilitation strategies evolve in the future. J Orthop Sports Phys Ther 2002;32:65-74.

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“…Indeed, the expression of these structural genes is not correlated with the presence of their specific activator because the embryonic/larval isoforms of MHC and ␤-TM appear at stages 21 and 25, respectively, when there is still no myogenin expression, and the adult isoforms of MHC appear at stage 52, when only XmyogU2 is expressed. This findings are consistent with previous studies showing that the relationship between MRF and MHC expression is not causal (49). It can be speculated that the activation of expression of these structural genes by myogenin in Xenopus takes place in adult tissues in the maintenance of a particular phenotype and during the muscle-regenerating process.…”

Section: Restricted Expression Of Myogenin In Oxidative Myofibers Of mentioning

confidence: 99%

Two Myogenin-related Genes Are Differentially Expressed inXenopus laevis Myogenesis and Differ in Their Ability to Transactivate Muscle Structural Genes

Charbonnier

Gaspera

Armand

et al. 2002

Journal of Biological Chemistry

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Among the myogenic regulatory factors, myogenin is a transcriptional activator situated at a crucial position for terminal differentiation in muscle development. It is unclear at present whether myogenin exhibits unique specificities to transactivate late muscular markers. During Xenopus development, the accumulation of myogenin mRNA is restricted to secondary myogenesis, at the onset of the appearance of adult isoforms of ␤-tropomyosin and myosin heavy chain. To determine the role of myogenin in the isoform switch of these contractile proteins, we characterized and directly compared the functional properties of myogenin with other myogenic regulatory factors in Xenopus embryos. Two distinct cDNAs related to myogenin, XmyogU1 and XmyogU2, were differentially expressed during myogenesis and in adult tissues, in which they preferentially accumulated in oxidative myofibers. Animal cap assays in Xenopus embryos revealed that myogenin, but not the other myogenic regulatory factors, induced expression of embryonic/larval isoforms of the ␤-tropomyosin and myosin heavy chain genes. Only XmyogU1 induced expression of the adult fast isoform of the myosin heavy chain gene. This is the first demonstration of a specific transactivation of one set of muscle structural genes by myogenin.The members of the MyoD gene family, including myoD (1), myogenin (2), myf5 (3), and MRF4 (4, 5), encode myogenic transcription factors (MRFs) 1 able to convert non-muscle cells to a muscle phenotype in culture (6, 7). First identified in mammals, all four proteins share a highly conserved central region related to the basic helix-loop-helix domain of the c-Myc superfamily. The MRFs are specifically expressed in skeletal muscle, with non-identical patterns of expression (8), and form a regulatory network controlling muscle determination and/or differentiation. Experiments using various MRF knockout mice have progressively elucidated the hierarchical relationships among the MRFs and established that functional redundancy is a feature of the MRF regulatory network. Thus, MyoD and Myf5 play overlapping roles in myoblast specification, whereas myogenin and either MyoD or MRF4 are required for differentiation (9). However, the redundant functions of MyoD and MRF4 appear not to overlap with those of myogenin (10). Knockout mice lacking the myogenin gene die at birth due to severe muscle deficiency, despite normal levels of MyoD and Myf5 (11,12). Recent studies have shown that the role of myogenin in muscle formation is distinct from that of MyoD and that this difference is due to functional specialization, and not just regulation of expression (13,14).Surprisingly little is known about the identity of muscle genes that are selectively activated by myogenin and that cannot be activated by the other myogenic regulators. Indeed, all the MRFs can transactivate muscle-specific gene expression by interacting with the consensus nucleotide motif, CANNTG, also called the E box, and they are all believed to bind to their target sequences as heterodimers with ...

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Myosin heavy chain isoform expression following reduced neuromuscular activity: Potential regulatory mechanisms

Cited by 251 publications

References 156 publications

High Level of Uncoupling Protein 1 Expression in Muscle of Transgenic Mice Selectively Affects Muscles at Rest and Decreases Their IIb Fiber Content

High Level of Uncoupling Protein 1 Expression in Muscle of Transgenic Mice Selectively Affects Muscles at Rest and Decreases Their IIb Fiber Content

Muscular, Skeletal, and Neural Adaptations Following Spinal Cord Injury

Two Myogenin-related Genes Are Differentially Expressed inXenopus laevis Myogenesis and Differ in Their Ability to Transactivate Muscle Structural Genes

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