Molecular basis of skeletal muscle plasticity-from gene to form and function

Abstract

Skeletal muscle shows an enormous plasticity to adapt to stimuli such as contractile activity (endurance exercise, electrical stimulation, denervation), loading conditions (resistance training, microgravity), substrate supply (nutritional interventions) or environmental factors (hypoxia). The presented data show that adaptive structural events occur in both muscle fibres (myofibrils, mitochondria) and associated structures (motoneurons and capillaries). Functional adaptations appear to involve alterations in regulatory mechanisms (neuronal, endocrine and intracellular signalling), contractile properties and metabolic capacities. With the appropriate molecular techniques it has been demonstrated over the past 10 years that rapid changes in skeletal muscle mRNA expression occur with exercise in human and rodent species. Recently, gene expression profiling analysis has demonstrated that transcriptional adaptations in skeletal muscle due to changes in loading involve a broad range of genes and that mRNA changes often run parallel for genes in the same functional categories. These changes can be matched to the structural/functional adaptations known to occur with corresponding stimuli. Several signalling pathways involving cytoplasmic protein kinases and nuclear-encoded transcription factors are recognized as potential master regulators that transduce physiological stress into transcriptional adaptations of batteries of metabolic and contractile genes. Nuclear reprogramming is recognized as an important event in muscle plasticity and may be related to the adaptations in the myosin type, protein turnover, and the cytoplasma-to-myonucleus ratio. The accessibility of muscle tissue to biopsies in conjunction with the advent of high-throughput gene expression analysis technology points to skeletal muscle plasticity as a particularly useful paradigm for studying gene regulatory phenomena in humans.Structure, function: bOX b-Oxidation · DEL Deltoidus · EC coupling Excitationcontraction coupling · EDL Extensor digitorum longus · Gls Glycolysis · H+ Reducing equivalents · IMF mitochondria Interfibrillar mitochondria · IMCL Intra-myocellular lipid · KC Krebs cycle · M Muscle · NMJ Neuromuscular junction · SR Sarcoplasmic reticulum · S mitochondria Subsarcolemmal mitochondria · Tn Troponin · VL Vastus lateralis · VO2max Maximal oxygen consumption Signals, sensors and transducers: ACTH Corticotropin · AMPK 5'-AMP-activated protein kinase · ATP Adenosine 5'-triphosphate · Ca2+ Intracellular calcium · CaMKII Ca 2+ /CaM kinase II · Cor Cortisol · EN Epinephrine · ERK Extracellular signal-regulated kinase · GH Growth hormone · IGFBP-3 Insulin-like growth factor binding protein 3 · IGF-I Insulin-like growth factor I · JNK c-jun N-terminal kinase · c-jun cellular counterpart of retroviral insert from avian sarcoma virus 17 · Ins Insulin · lep Leptin · MAPK Mitogen-activated (microtubule-associated) protein kinase · NRF-1 and -2 Nuclear respiratory factor 1 and 2 · p38 p38 MAPK · RE Renin · ROS Reactive oxygen species · T3 Triiodothyron...

Are cultured human myotubes far from home?

“…The experimental model of chronic low-frequency stimulation (CLF) in animals has shown such transitions in rabbits and rats (for review see (Pette and Vrbova, 1999)). The plasticity of skeletal muscle in general has been thoroughly reviewed by others (Fluck and Hoppeler, 2003, Gundersen, 2010, Schiaffino and Reggiani, 2011.…”

Statin or fibrate chronic treatment modifies the proteomic profile of rat skeletal muscle

“…increased expression of fast isoforms of myosin heavy chain (MHC) and increase of resting gCl in soleus muscle [40]. A coordinated expression existed among MHC isoforms, metabolic enzymes and isoforms of other myofibrillar and non-myofibrillar proteins [41][42][43]. Therefore, in most myopathic conditions the change in expression of many proteins can be related to the activation of a single gene expression program aimed to coordinately adapt muscle contractile machinery, energy production and cytoskeleton.…”

Recovery of skeletal muscle mass after extensive injury: positive effects of increased contractile activity

“…The maturation of regenerating fibers appears to be under the influence of numerous external factors, among them neural influence (38,46) and mechanical loading (13). Because muscle contractile activity involves biological signals related to both motor nerve activity and mechanical stress (17), it is logical to speculate that physical activity should have beneficial effects on muscle growth. This putative beneficial effect of contractile activity has been previously examined during regeneration after either grafting (47) or myotoxic-induced muscle degeneration (14).…”