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

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

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.

Abbreviations

Stimuli

CLFS

Chronic low-frequency electric stimulation

CR

Caloric restriction

DE

Detraining

DV

Denervation

EE

Endurance exercise

ER

Endurance runners

I

Immobilization

IN

Inactivity

MG

Real or simulated microgravity

RT

Resistance training

WL

Weightlifters

Structure, function

βOX

β-Oxidation

DEL

Deltoidus

EC coupling

Excitation-contraction 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 consumptioin

Signals, sensors and transducers

ACTH

Corticotropin

AMPK

5’-AMO-activated protein kinase

ATP

Adempsome 5’-triphosphate

Ca2+

Intracellular calcium

CaMKII

Ca2+/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

Triiodothyronine

T4

Tetraiodothyronine

Tes

Testosterone

TFAM

Mitochondiral transcription factor

TSH

Thyroid stimulating hormone

Genes

3’UTR

3’ Untranslated region

5’UTR

5’ Untranslated region

ACAA2

3-ketoacyl-CoA thiolase

ACC

Acetyl-CoA carboxylase

AIF1

Allograft inflammatory factor 1

AOX1

Aldehyde oxidase

ATP5A

ATP synthase alpha chain

ATP5C

ATP synthase gamma chain

ATP5G3

ATP synthase lipid-binding protein

ATP5J

ATP synthase coupling factor 6

ATPB

ATP synthase beta chain

Cat H

Cathepsin H

CDC16Hs

Cell division cycle 16

c-fos

c-fos Proto-oncogene

c-jun

c-jun Protooncogene

CK

Creatine kinase

Col

Collagen type

CPT I and II

Carnitine O-palmitoyltransferases I and II

COX

Cytochrome C oxidase subunits

CSF-1

Colony stimulating factor

CXCL5

Small inducible cytokine B5

CYP2A6

Cytochrome P450 2A6

CYP2B6

Cytochrome P450 2B6

CYP2C8

Cytochrome P450 2C8

CYPdb1

Cytochrome P450 db1

DDO

d-aspartate oxidase

DIA1

NADH-cytochrome b5 reductase

DNA

Deoxyribonucleic acid

DP5

Neuronal death protein

EGFR

Epidermal growth factor receptor

ERF

Ets2 repressor factor

FAP

Fibroblast activation protein

FAT/CD36

Fatty acid translocase

FBP2

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

FN

Fibronectin

Fum

Fumarase

gamma 1

Interferon gamma treatment inducible mRNA

glut-1

Glucose transporter 1

HIAP1

Inhibitor of apoptosis protein 1

HIF-1α

Hypoxia-inducible factor 1 alpha

HPARG

Poly(ADP-ribose) glycohydrolase

HPXEL

Peroxisomal enoyl-CoA hydratase-like protein

HSC

Heat shock cognate

HSP

Heat shock protein

HSP27 and 70

Heat shock protein 27 and 70

HSP2

Heparan sulfate proteoglycan 2

IL-1, -12 and -18

Interleukin 1, 12 and 18

IMPDH1

Inosine-5’-monophosphate dehydrogenase 1

LDH

lactate dehydrogenase

LIF

Leukaemia inhibitory factor precursor

LN

Laminin

LPL

Lipoprotein lipase

LRP1

Low-density lipoprotein receptor-related protein 1

LTC4S

Human leucotriene C4 synthase

Mac-2

Macrophage subpopulation-specific antigen 2

MARK3

MAP/microtubule affinityregulating kinase 3 long

MAT1

CDK-activating kinase assembly factor

MCAD

Medium chain-specific acyl-CoA dehydrogenase

MCT1, 2 and 4

Monocarboxylate transporters 1, 2 and 4

MHC

Myosin heavy chain

MHC10

Nonmuscle type B myosin heavy chain (MYH10)

MHC9

Nonmuscle type A myosin heavy chain (MYH9)

mRNA

Messenger ribonucleic acid

MSH3

DNA mismatch repair protein

MT1B

Metallothionein-IB

MT1F

Metallothionein I F

MEF2

Myocyte enhancer factor 2

myoD

Myoblast determination protein

MRF4

Muscle regulatory factor 4

myf 5 and 6

Myogenic factors 5 and 6

nAChR

Nicotinic acetyl choline receptor

NADH6

Mitochondrially-encoded NADH dehydrogenase subunit

NF-kappa B

Nuclear factor kappa B

NCAM1

Neural cell adhesion molecule 1

NDUFV1

NADH-ubiquinone oxidoreductase 51 kDa subunit

NDUFV2

NADH-ubiquinone oxidoreductase 24 kDa subunit complex core protein 2

NF-kB p65

Nuclear factor kappa B p65 subunit

NF-Y

Nuclear factor Y protein subunit A

NNT

Mitochondrial NAD(P) transhydrogenase

NRG-1

Neuregulin

ORP150

150 kDa Oxygen-regulated protein

p21

Cyclin-dependent kinase inhibitor 1

PON2

Paraoxonase 2

PDK4

Pyruvate dehydrogenase kinase 4

PP2Ag1

Serine/threonine protein phosphatase 2A

PPAR

Peroxisome proliferator-activated receptor

RANTES

Regulated upon activation, normal T cell expressed and secreted

RECQ2

RecQ-like type 2 DNA helicase

RNA

Ribonucleic acid

RYK

Related to receptor tyrosine kinase

SCHAD

Short chain 3-hydroxyacyl-CoA dehydrogenase

SDH

Succinate dehydrogenase

SH3GL3

SH3-containing GRB2-like protein 3

SOD2

Manganese superoxide dismutase

SVCT2

Sodium-dependent vitamin C transporter

tie 2

Angiopoietin 1 receptor

TRAP230

Thyroid hormone receptor-associated protein complex component

TSP4

Thrombospondin 4

UCP

Mitochondrial uncoupling protein

UQCRB

Ubiquinol-cytochrome C reductase

UQCRC2

Ubiquinol-cytochrome C reductase

UQCRH

Ubiquinol-cytochrome C reductase complex 11 kDa protein

VEGF

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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