The FASEB Journal express article 10.1096/fj.04-3149fje. Published online June 28, 2005. Analysis of global mRNA expression in human skeletal muscle during recovery from endurance exercise

To search for novel transcriptional pathways that are activated in skeletal muscle after endurance exercise, we used cDNA microarrays to measure global mRNA expression after an exhaustive bout of high‐intensity cycling (∼75 min). Healthy, young, sedentary males performed the cycling bout, and skeletal muscle biopsies were taken from the vastus lateralis before, and at 3 and 48 h after exercise. We examined mRNA expression in individual muscle samples from four subjects using cDNA microarrays, used repeated‐measures significance analysis of microarray (SAM) to determine statistically significant expression changes, and confirmed selected results using real‐time RT‐PCR. In total, the expression of 118 genes significantly increased 3 h postcycling and 8 decreased. At 48 h, the expression of 29 genes significantly increased and 5 decreased. Many of these are potentially important novel genes involved in exercise recovery and adaptation, including several involved in 1) metabolism and mitochondrial biogenesis (FOXO1, PPARδ, PPARγ, nuclear receptor binding protein 2, IL‐6 receptor, ribosomal protein L2, aminolevulinate δ‐synthase 2); 2) the oxidant stress response (metalothioneins 1B, 1F, 1G, 1H, 1L, 2A, 3, interferon regulatory factor 1); and 3) electrolyte transport across membranes [Na+‐K+‐ATPase (β3), SERCA3, chloride channel 4]. Others include genes involved in cell stress, proteolysis, apoptosis, growth, differentiation, and transcriptional activation, as well as all three nuclear receptor subfamily 4A family members (Nur77, Nurr1, and Nor1). This study is the first to characterize global mRNA expression during recovery from endurance exercise, and the results provide potential insight into 1) the transcriptional contributions to homeostatic recovery in human skeletal muscle after endurance exercise, and 2) the transcriptional contributions from a single bout of endurance exercise to the adaptive processes that occur after a period of endurance exercise training.

[1]  B. Pedersen,et al.  Exercise‐induced metallothionein expression in human skeletal muscle fibres , 2005, Experimental physiology.

[2]  P. Schjerling,et al.  The FASEB Journal express article 10.1096/fj.04-2084fje. Published online October 29, 2004. Are exercise-induced genes induced by exercise? , 2022 .

[3]  B. Saltin,et al.  Endurance training reduces the contraction-induced interleukin-6 mRNA expression in human skeletal muscle. , 2004, American journal of physiology. Endocrinology and metabolism.

[4]  M. Bray,et al.  Diurnal variations in the responsiveness of cardiac and skeletal muscle to fatty acids. , 2004, American journal of physiology. Endocrinology and metabolism.

[5]  M. McKenna,et al.  Prolonged exercise to fatigue in humans impairs skeletal muscle Na+-K+-ATPase activity, sarcoplasmic reticulum Ca2+ release, and Ca2+ uptake. , 2004, Journal of applied physiology.

[6]  P. Schjerling,et al.  Lipid-binding proteins and lipoprotein lipase activity in human skeletal muscle: influence of physical activity and gender. , 2004, Journal of applied physiology.

[7]  Hiroyuki Aburatani,et al.  Skeletal Muscle FOXO1 (FKHR) Transgenic Mice Have Less Skeletal Muscle Mass, Down-regulated Type I (Slow Twitch/Red Muscle) Fiber Genes, and Impaired Glycemic Control*[boxs] , 2004, Journal of Biological Chemistry.

[8]  Kathleen Y. Lee,et al.  Gene expression profiling in mitochondrial disease: assessment of microarray accuracy by high-throughput Q-PCR. , 2004, Mitochondrion.

[9]  R. Evans,et al.  Regulation of Muscle Fiber Type and Running Endurance by PPARδ , 2004, PLoS biology.

[10]  M. Tarnopolsky,et al.  Real-time RT-PCR analysis of housekeeping genes in human skeletal muscle following acute exercise. , 2004, Physiological genomics.

[11]  M. Febbraio,et al.  Interleukin-6 is a novel factor mediating glucose homeostasis during skeletal muscle contraction. , 2004, Diabetes.

[12]  J. Fowles,et al.  Malleability of human skeletal muscle Na(+)-K(+)-ATPase pump with short-term training. , 2004, Journal of applied physiology.

[13]  H. Green Membrane excitability, weakness, and fatigue. , 2004, Canadian journal of applied physiology = Revue canadienne de physiologie appliquee.

[14]  S. Cairns,et al.  Protective role of extracellular chloride in fatigue of isolated mammalian skeletal muscle. , 2004, American journal of physiology. Cell physiology.

[15]  D. Accili,et al.  FoxOs at the Crossroads of Cellular Metabolism, Differentiation, and Transformation , 2004, Cell.

[16]  J. Helge,et al.  Symposium 2 : The fatty acid transporters of skeletal muscle Studies of plasma membrane fatty acid-binding protein and other lipid-binding proteins in human skeletal muscle , 2004 .

[17]  P. Neufer,et al.  Transcriptional regulation of pyruvate dehydrogenase kinase 4 in skeletal muscle during and after exercise , 2004, The Proceedings of the Nutrition Society.

[18]  Robert A. Harris,et al.  Protein kinase B-alpha inhibits human pyruvate dehydrogenase kinase-4 gene induction by dexamethasone through inactivation of FOXO transcription factors. , 2004, Diabetes.

[19]  M. McKenna,et al.  Intense exercise up‐regulates Na+,K+‐ATPase isoform mRNA, but not protein expression in human skeletal muscle , 2004, The Journal of physiology.

[20]  R. Billeter,et al.  Regulatory gene expression in skeletal muscle of highly endurance-trained humans. , 2004, Acta physiologica Scandinavica.

[21]  P. Ferré,et al.  The biology of peroxisome proliferator-activated receptors: relationship with lipid metabolism and insulin sensitivity. , 2004, Diabetes.

[22]  R. Lieber,et al.  Rapid muscle-specific gene expression changes after a single bout of eccentric contractions in the mouse. , 2004, American journal of physiology. Cell physiology.

[23]  Rong-yu Li,et al.  Systematic comparison of the fidelity of aRNA, mRNA and T-RNA on gene expression profiling using cDNA microarray. , 2004, Journal of biotechnology.

[24]  S. Stannard,et al.  Muscle Triglyceride and Glycogen in Endurance Exercise , 2004, Sports medicine.

[25]  W. Kraus,et al.  PGC-1alpha mRNA expression is influenced by metabolic perturbation in exercising human skeletal muscle. , 2004, Journal of applied physiology.

[26]  A. Sugawara,et al.  Regulation of skeletal muscle peroxisome proliferator-activated receptor gamma expression by exercise and angiotensin-converting enzyme inhibition in fructose-fed hypertensive rats. , 2004, Hypertension research : official journal of the Japanese Society of Hypertension.

[27]  L. Goodyear,et al.  5’ Adenosine Monophosphate-Activated Protein Kinase, Metabolism and Exercise , 2004, Sports medicine.

[28]  W. Kraus,et al.  PGC-1α mRNA expression is influenced by metabolic perturbation in exercising human skeletal muscle , 2004 .

[29]  T. Takala,et al.  Regulation of type IV collagen gene expression and degradation in fast and slow muscles during dexamethasone treatment and exercise , 2004, Pflügers Archiv.

[30]  J. Koropatnick,et al.  Signaling events for metallothionein induction. , 2003, Mutation research.

[31]  A. Russell,et al.  Endurance training in humans leads to fiber type-specific increases in levels of peroxisome proliferator-activated receptor-gamma coactivator-1 and peroxisome proliferator-activated receptor-alpha in skeletal muscle. , 2003, Diabetes.

[32]  Eric P Hoffman,et al.  Molecular responses of human muscle to eccentric exercise. , 2003, Journal of applied physiology.

[33]  A. Jeukendrup Modulation of carbohydrate and fat utilization by diet, exercise and environment. , 2003, Biochemical Society transactions.

[34]  M. Lane,et al.  Convergence of Peroxisome Proliferator-activated Receptor γ and Foxo1 Signaling Pathways* , 2003, Journal of Biological Chemistry.

[35]  I. Kohane,et al.  Gene expression profile after cardiopulmonary bypass and cardioplegic arrest. , 2003, The Journal of thoracic and cardiovascular surgery.

[36]  A. Steensberg,et al.  Interleukin-6 production by contracting human skeletal muscle: autocrine regulation by IL-6. , 2003, Biochemical and biophysical research communications.

[37]  T. Furuyama,et al.  Forkhead transcription factor FOXO1 (FKHR)-dependent induction of PDK4 gene expression in skeletal muscle during energy deprivation. , 2003, The Biochemical journal.

[38]  Jourdan J. Pouliot,et al.  development and , 2019 .

[39]  Nathan Salomonis,et al.  Time- and exercise-dependent gene regulation in human skeletal muscle , 2003, Genome Biology.

[40]  B. Spiegelman,et al.  Muscle-specific PPARgamma-deficient mice develop increased adiposity and insulin resistance but respond to thiazolidinediones. , 2003, The Journal of clinical investigation.

[41]  H. Green,et al.  Paradoxical effects of prior activity on human sarcoplasmic reticulum Ca2+-ATPase response to exercise. , 2003, Journal of applied physiology.

[42]  Sophie Rome,et al.  Microarray Profiling of Human Skeletal Muscle Reveals That Insulin Regulates ∼800 Genes during a Hyperinsulinemic Clamp* 210 , 2003, The Journal of Biological Chemistry.

[43]  M. Tarnopolsky,et al.  Adaptations in human muscle sarcoplasmic reticulum to prolonged submaximal training. , 2003, Journal of applied physiology.

[44]  Miki Suzuki,et al.  A forkhead transcription factor FKHR up‐regulates lipoprotein lipase expression in skeletal muscle , 2003, FEBS letters.

[45]  Henriette Pilegaard,et al.  Exercise induces transient transcriptional activation of the PGC‐1α gene in human skeletal muscle , 2003, The Journal of physiology.

[46]  P. Puigserver,et al.  Peroxisome proliferator-activated receptor-gamma coactivator 1 alpha (PGC-1 alpha): transcriptional coactivator and metabolic regulator. , 2003, Endocrine reviews.

[47]  D. Hood,et al.  Plasticity of Skeletal Muscle Mitochondria in Response to Contractile Activity , 2003, Experimental physiology.

[48]  M. Lane,et al.  Convergence of peroxisome proliferator-activated receptor gamma and Foxo1 signaling pathways. , 2003, The Journal of biological chemistry.

[49]  Sophie Rome,et al.  Microarray profiling of human skeletal muscle reveals that insulin regulates approximately 800 genes during a hyperinsulinemic clamp. , 2003, The Journal of biological chemistry.

[50]  E Fehrenbach,et al.  Microarray technology--the future analyses tool in exercise physiology? , 2003, Exercise immunology review.

[51]  Eric P Hoffman,et al.  Response of rat muscle to acute resistance exercise defined by transcriptional and translational profiling , 2002, The Journal of physiology.

[52]  J. Fowles,et al.  Reduced activity of muscle Na(+)-K(+)-ATPase after prolonged running in rats. , 2002, Journal of applied physiology.

[53]  K. Hahm,et al.  Protective effect of metallothionein-III on DNA damage in response to reactive oxygen species. , 2002, Biochimica et biophysica acta.

[54]  E. Metter,et al.  Influence of age, sex, and strength training on human muscle gene expression determined by microarray. , 2002, Physiological genomics.

[55]  G. Wadley,et al.  Exercise training increases lipid metabolism gene expression in human skeletal muscle. , 2002, American journal of physiology. Endocrinology and metabolism.

[56]  D. Littman,et al.  Nuclear Hormone Receptors in T Lymphocytes , 2002, Cell.

[57]  L. Ji Exercise‐induced Modulation of Antioxidant Defense , 2002, Annals of the New York Academy of Sciences.

[58]  J. Reecy,et al.  Differential gene expression in the rat soleus muscle during early work overload‐induced hypertrophy , 2002, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[59]  M. Heller DNA microarray technology: devices, systems, and applications. , 2002, Annual review of biomedical engineering.

[60]  E. Hoffman,et al.  Sources of variability and effect of experimental approach on expression profiling data interpretation , 2002, BMC Bioinformatics.

[61]  Thomas D. Schmittgen,et al.  Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. , 2001, Methods.

[62]  P. Neufer,et al.  Transcriptional activation of the IL‐6 gene in human contracting skeletal muscle: influence of muscle glycogen content , 2001, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[63]  M. Kondoh,et al.  Specific induction of metallothionein synthesis by mitochondrial oxidative stress. , 2001, Life sciences.

[64]  W. Derave,et al.  Glucose, exercise and insulin: emerging concepts , 2001, The Journal of physiology.

[65]  L. Ji,et al.  Superoxide dismutase gene expression is activated by a single bout of exercise in rat skeletal muscle , 2001, Pflügers Archiv.

[66]  M. Tarnopolsky,et al.  Substrate utilization during endurance exercise in men and women after endurance training. , 2001, American journal of physiology. Endocrinology and metabolism.

[67]  R. Tibshirani,et al.  Significance analysis of microarrays applied to the ionizing radiation response , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[68]  G. Cooney,et al.  Expression of genes involved in lipid metabolism correlate with peroxisome proliferator-activated receptor gamma expression in human skeletal muscle. , 2000, The Journal of clinical endocrinology and metabolism.

[69]  P. Neufer,et al.  Transcriptional regulation of gene expression in human skeletal muscle during recovery from exercise. , 2000, American journal of physiology. Endocrinology and metabolism.

[70]  T. Tsukamoto,et al.  Nuclear receptor binding factor-2 (NRBF-2), a possible gene activator protein interacting with nuclear hormone receptors. , 2000, Biochimica et biophysica acta.

[71]  O. Boss,et al.  Expression of peroxisome proliferator-activated receptors in lean and obese Zucker rats. , 2000, European journal of endocrinology.

[72]  F. Marumo,et al.  Identification of an acid-activated Cl(-) channel from human skeletal muscles. , 1999, The American journal of physiology.

[73]  B. E. Murray,et al.  Effects of chronic low-frequency stimulation on Ca2+-regulatory membrane proteins in rabbit fast muscle , 1999, Pflügers Archiv.

[74]  A. Bonen,et al.  Muscle contractile activity increases fatty acid metabolism and transport and FAT/CD36. , 1999, American journal of physiology. Endocrinology and metabolism.

[75]  J. Ivy,et al.  Regulation of GLUT4 protein expression and glycogen storage after prolonged exercise. , 1999, Acta physiologica Scandinavica.

[76]  M. Sokabe,et al.  Induction of nuclear respiratory factor-1 expression by an acute bout of exercise in rat muscle. , 1998, Biochimica et biophysica acta.

[77]  W. Maret,et al.  Thiolate ligands in metallothionein confer redox activity on zinc clusters. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[78]  P. Puigserver,et al.  A Cold-Inducible Coactivator of Nuclear Receptors Linked to Adaptive Thermogenesis , 1998, Cell.

[79]  J. Davis,et al.  Carbohydrate and the cytokine response to 2.5 h of running. , 1997, Journal of applied physiology.

[80]  Mi-Ock Lee,et al.  Modulation of retinoic acid sensitivity in lung cancer cells through dynamic balance of orphan receptors nur77 and COUP‐TF and their heterodimerization , 1997, The EMBO journal.

[81]  P. Neufer,et al.  Continuous contractile activity induces fiber type specific expression of HSP70 in skeletal muscle. , 1996, The American journal of physiology.

[82]  Luchuan Liang,et al.  Oxidative Stress Activates Metal-responsive Transcription Factor-1 Binding Activity , 1996, The Journal of Biological Chemistry.

[83]  D. Petering,et al.  Direct reaction of H2O2 with sulfhydryl groups in HL-60 cells: zinc-metallothionein and other sites. , 1996, Archives of biochemistry and biophysics.

[84]  W. Wahli,et al.  Peroxisome proliferator activated receptors: transcriptional regulators of adipogenesis, lipid metabolism and more.... , 1995, Chemistry & biology.

[85]  J. Lazo,et al.  Enhanced Sensitivity to Oxidative Stress in Cultured Embryonic Cells from Transgenic Mice Deficient in Metallothionein I and II Genes (*) , 1995, The Journal of Biological Chemistry.

[86]  J. Holloszy,et al.  Exercise induces rapid increases in GLUT4 expression, glucose transport capacity, and insulin-stimulated glycogen storage in muscle. , 1994, The Journal of biological chemistry.

[87]  Y. Liu,et al.  Increase in metallothionein produced by chemicals that induce oxidative stress. , 1991, Toxicology and applied pharmacology.

[88]  G. Heigenhauser,et al.  Ion fluxes during tetanic stimulation in isolated perfused rat hindlimb. , 1988, The American journal of physiology.

[89]  G. Dohm,et al.  Protein degradation during endurance exercise and recovery. , 1987, Medicine and science in sports and exercise.

[90]  Paul J Thornalley,et al.  Possible role for metallothionein in protection against radiation-induced oxidative stress. Kinetics and mechanism of its reaction with superoxide and hydroxyl radicals. , 1985, Biochimica et biophysica acta.