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

Part of the Reviews of Physiology, Biochemistry and Pharmacology book series (REVIEWS, volume 146)


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.




Chronic low-frequency electric stimulation


Caloric restriction






Endurance exercise


Endurance runners






Real or simulated microgravity


Resistance training



Structure, function





EC coupling

Excitation-contraction coupling


Extensor digitorum longus




Reducing equivalents

IMF mitochondria

Interfibrillar mitochondria


Intra-myocellular lipid


Krebs cycle




Neuromuscular junction


Sarcoplasmic reticulum

S mitochondria

Subsarcolemmal mitochondria




Vastus lateralis


Maximal oxygen consumptioin

Signals, sensors and transducers




5’-AMO-activated protein kinase


Adempsome 5’-triphosphate


Intracellular calcium


Ca2+/CaM kinase II






Extracellular signal-regulated kinase


Growth hormone


Insulin-like growth factor binding protein 3


Insulin-like growth factor I


c-jun N-terminal kinase


cellular counterpart of retroviral insert from avian sarcoma virus 17






Mitogen-activated (microtubule-associated) protein kinase

NRF-1 and 2

Nuclear respiratory factor 1 and 2


p38 MAPK




Reactive oxygen species








Mitochondiral transcription factor


Thyroid stimulating hormone



3’ Untranslated region


5’ Untranslated region


3-ketoacyl-CoA thiolase


Acetyl-CoA carboxylase


Allograft inflammatory factor 1


Aldehyde oxidase


ATP synthase alpha chain


ATP synthase gamma chain


ATP synthase lipid-binding protein


ATP synthase coupling factor 6


ATP synthase beta chain

Cat H

Cathepsin H


Cell division cycle 16


c-fos Proto-oncogene


c-jun Protooncogene


Creatine kinase


Collagen type

CPT I and II

Carnitine O-palmitoyltransferases I and II


Cytochrome C oxidase subunits


Colony stimulating factor


Small inducible cytokine B5


Cytochrome P450 2A6


Cytochrome P450 2B6


Cytochrome P450 2C8


Cytochrome P450 db1


d-aspartate oxidase


NADH-cytochrome b5 reductase


Deoxyribonucleic acid


Neuronal death protein


Epidermal growth factor receptor


Ets2 repressor factor


Fibroblast activation protein


Fatty acid translocase


d-fructose-1,6-bisphosphate 1-phosphohydrolase





gamma 1

Interferon gamma treatment inducible mRNA


Glucose transporter 1


Inhibitor of apoptosis protein 1


Hypoxia-inducible factor 1 alpha


Poly(ADP-ribose) glycohydrolase


Peroxisomal enoyl-CoA hydratase-like protein


Heat shock cognate


Heat shock protein

HSP27 and 70

Heat shock protein 27 and 70


Heparan sulfate proteoglycan 2

IL-1, -12 and -18

Interleukin 1, 12 and 18


Inosine-5’-monophosphate dehydrogenase 1


lactate dehydrogenase


Leukaemia inhibitory factor precursor




Lipoprotein lipase


Low-density lipoprotein receptor-related protein 1


Human leucotriene C4 synthase


Macrophage subpopulation-specific antigen 2


MAP/microtubule affinityregulating kinase 3 long


CDK-activating kinase assembly factor


Medium chain-specific acyl-CoA dehydrogenase

MCT1, 2 and 4

Monocarboxylate transporters 1, 2 and 4


Myosin heavy chain


Nonmuscle type B myosin heavy chain (MYH10)


Nonmuscle type A myosin heavy chain (MYH9)


Messenger ribonucleic acid


DNA mismatch repair protein




Metallothionein I F


Myocyte enhancer factor 2


Myoblast determination protein


Muscle regulatory factor 4

myf 5 and 6

Myogenic factors 5 and 6


Nicotinic acetyl choline receptor


Mitochondrially-encoded NADH dehydrogenase subunit

NF-kappa B

Nuclear factor kappa B


Neural cell adhesion molecule 1


NADH-ubiquinone oxidoreductase 51 kDa subunit


NADH-ubiquinone oxidoreductase 24 kDa subunit complex core protein 2

NF-kB p65

Nuclear factor kappa B p65 subunit


Nuclear factor Y protein subunit A


Mitochondrial NAD(P) transhydrogenase




150 kDa Oxygen-regulated protein


Cyclin-dependent kinase inhibitor 1


Paraoxonase 2


Pyruvate dehydrogenase kinase 4


Serine/threonine protein phosphatase 2A


Peroxisome proliferator-activated receptor


Regulated upon activation, normal T cell expressed and secreted


RecQ-like type 2 DNA helicase


Ribonucleic acid


Related to receptor tyrosine kinase


Short chain 3-hydroxyacyl-CoA dehydrogenase


Succinate dehydrogenase


SH3-containing GRB2-like protein 3


Manganese superoxide dismutase


Sodium-dependent vitamin C transporter

tie 2

Angiopoietin 1 receptor


Thyroid hormone receptor-associated protein complex component


Thrombospondin 4


Mitochondrial uncoupling protein


Ubiquinol-cytochrome C reductase


Ubiquinol-cytochrome C reductase


Ubiquinol-cytochrome C reductase complex 11 kDa protein


Vascular endothelial growth factor


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© Springer-Verlagb 2003

Authors and Affiliations

  1. 1.Institute of AnatomyUniversity of BernBern 9Switzerland

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