Time- and exercise-dependent gene regulation in human skeletal muscle

BackgroundSkeletal muscle remodeling is a critical component of an organism's response to environmental changes. Exercise causes structural changes in muscle and can induce phase shifts in circadian rhythms, fluctuations in physiology and behavior with a period of around 24 hours that are maintained by a core clock mechanism. Both exercise-induced remodeling and circadian rhythms rely on the transcriptional regulation of key genes.ResultsWe used DNA microarrays to determine the effects of resistance exercise (RE) on gene regulation in biopsy samples of human quadriceps muscle obtained 6 and 18 hours after an acute bout of isotonic exercise with one leg. We also profiled diurnal gene regulation at the same time points (2000 and 0800 hours) in the non-exercised leg. Comparison of our results with published circadian gene profiles in mice identified 44 putative genes that were regulated in a circadian fashion. We then used quantitative PCR to validate the circadian expression of selected gene orthologs in mouse skeletal muscle.ConclusionsThe coordinated regulation of the circadian clock genes Cry1, Per2, and Bmal1 6 hours after RE and diurnal genes 18 hours after RE in the exercised leg suggest that RE may directly modulate circadian rhythms in human skeletal muscle.

[1]  S. Kay,et al.  Molecular bases of circadian rhythms. , 2001, Annual review of cell and developmental biology.

[2]  I. Piña,et al.  AHA Science Advisory. Resistance exercise in individuals with and without cardiovascular disease: benefits, rationale, safety, and prescription: An advisory from the Committee on Exercise, Rehabilitation, and Prevention, Council on Clinical Cardiology, American Heart Association; Position paper endo , 2000, Circulation.

[3]  C. Tachi,et al.  Content and localization of myostatin in mouse skeletal muscles during aging, mechanical unloading and reloading , 2004, Journal of Muscle Research & Cell Motility.

[4]  G. Pertea,et al.  RESOURCERER: a database for annotating and linking microarray resources within and across species , 2001, Genome Biology.

[5]  B. H. Miller,et al.  Coordinated Transcription of Key Pathways in the Mouse by the Circadian Clock , 2002, Cell.

[6]  Charmane I. Eastman,et al.  Phase-shifting human circadian rhythms with exercise during the night shift , 1995, Physiology & Behavior.

[7]  E. Pease,et al.  Induction of mitogen-inducible nuclear orphan receptor by interleukin 1 in human synovial and gingival fibroblasts. , 1998, Biochemical and biophysical research communications.

[8]  J. Takahashi,et al.  Circadian rhythms: The cancer connection , 2002, Nature.

[9]  Peng Huang,et al.  The Circadian Gene Period2 Plays an Important Role in Tumor Suppression and DNA Damage Response In Vivo , 2002, Cell.

[10]  M. Byrne,et al.  Nocturnal exercise phase delays circadian rhythms of melatonin and thyrotropin secretion in normal men. , 1994, The American journal of physiology.

[11]  N. Mrosovsky,et al.  Rapid down-regulation of mammalian period genes during behavioral resetting of the circadian clock. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[12]  Ueli Schibler,et al.  The Orphan Nuclear Receptor REV-ERBα Controls Circadian Transcription within the Positive Limb of the Mammalian Circadian Oscillator , 2002, Cell.

[13]  C. Eastman,et al.  Intermittent bright light and exercise to entrain human circadian rhythms to night work. , 1999, The American journal of physiology.

[14]  R. Gomis,et al.  Mutation in the calcium-binding domain of the mitochondrial glycerophosphate dehydrogenase gene in a family of diabetic subjects. , 1997, Biochemical and biophysical research communications.

[15]  S. Matsufuji,et al.  Degradation of ornithine decarboxylase by the 26S proteasome. , 2000, Biochemical and biophysical research communications.

[16]  S. Reppert,et al.  Coordination of circadian timing in mammals , 2002, Nature.

[17]  E. van Cauter,et al.  Pathophysiology of human circadian rhythms. , 2000, Novartis Foundation symposium.

[18]  G. Skrinar,et al.  Plasma melatonin increases during exercise in women. , 1981, The Journal of clinical endocrinology and metabolism.

[19]  Thomas S. Kilduff,et al.  Influence of running wheel activity on free-running sleep/wake and drinking circadian rhythms in mice , 1991, Physiology & Behavior.

[20]  Steven M Reppert,et al.  mCRY1 and mCRY2 Are Essential Components of the Negative Limb of the Circadian Clock Feedback Loop , 1999, Cell.

[21]  W. Dement,et al.  Regularly scheduled voluntary exercise synchronizes the mouse circadian clock. , 1991, The American journal of physiology.

[22]  P. Pattany,et al.  Muscle fiber hypertrophy, hyperplasia, and capillary density in college men after resistance training. , 1996, Journal of applied physiology.

[23]  Kai-Florian Storch,et al.  Extensive and divergent circadian gene expression in liver and heart , 2002, Nature.

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

[25]  Y Sakaki,et al.  Entrainment of the circadian clock in the liver by feeding. , 2001, Science.

[26]  C. Kahn,et al.  Overexpression of Rad Inhibits Glucose Uptake in Cultured Muscle and Fat Cells* , 1996, The Journal of Biological Chemistry.

[27]  Rafael A Irizarry,et al.  Exploration, normalization, and summaries of high density oligonucleotide array probe level data. , 2003, Biostatistics.

[28]  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.

[29]  M Laguens,et al.  Circadian rhythm chaos: a new breast cancer marker. , 2001, International journal of fertility and women's medicine.

[30]  B. Langley,et al.  Myostatin Inhibits Myoblast Differentiation by Down-regulating MyoD Expression* , 2002, The Journal of Biological Chemistry.

[31]  C. Kahn,et al.  Rad: a member of the Ras family overexpressed in muscle of type II diabetic humans. , 1993, Science.

[32]  S. Mudaliar,et al.  Exercise adaptation attenuates VEGF gene expression in human skeletal muscle. , 2000, American journal of physiology. Heart and circulatory physiology.

[33]  Y. Matsubara,et al.  Molecular analysis of glycogen storage disease type Ib: identification of a prevalent mutation among Japanese patients and assignment of a putative glucose-6-phosphate translocase gene to chromosome 11. , 1998, Biochemical and biophysical research communications.

[34]  Steven C. Lawlor,et al.  GenMAPP, a new tool for viewing and analyzing microarray data on biological pathways , 2002, Nature Genetics.

[35]  W. Kraus,et al.  Exercise-induced angiogenesis-related growth and transcription factors in skeletal muscle, and their modification in muscle pathology. , 2001, Frontiers in bioscience : a journal and virtual library.

[36]  S. Rafii,et al.  Interleukin-1alpha promotes angiogenesis in vivo via VEGFR-2 pathway by inducing inflammatory cell VEGF synthesis and secretion. , 2002, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[37]  F. Fleury-Olela,et al.  Restricted feeding uncouples circadian oscillators in peripheral tissues from the central pacemaker in the suprachiasmatic nucleus. , 2000, Genes & development.

[38]  E. Olson,et al.  Defining the regulatory networks for muscle development. , 1996, Current opinion in genetics & development.

[39]  D. P. King,et al.  Molecular genetics of circadian rhythms in mammals. , 2000, Annual review of neuroscience.

[40]  I. Piña,et al.  Resistance Exercise in Individuals With and Without Cardiovascular Disease , 2000 .

[41]  W. Dement,et al.  Serotonergic afferents mediate activity-dependent entrainment of the mouse circadian clock. , 1997, The American journal of physiology.

[42]  Lukas Wagner,et al.  A Greedy Algorithm for Aligning DNA Sequences , 2000, J. Comput. Biol..

[43]  K. Esser,et al.  Phosphorylation of p70(S6k) correlates with increased skeletal muscle mass following resistance exercise. , 1999, The American journal of physiology.

[44]  S. Honma,et al.  Phase-advance shifts of human circadian pacemaker are accelerated by daytime physical exercise. , 2001, American journal of physiology. Regulatory, integrative and comparative physiology.

[45]  S. Rafii,et al.  Interleukin‐1α (IL‐1α) promotes angiogenesis in vivo via VEGFR‐2 pathway by inducing inflammatory cell VEGF synthesis and secretion , 2002 .

[46]  Toshiyuki Miyata,et al.  Herp, a New Ubiquitin-like Membrane Protein Induced by Endoplasmic Reticulum Stress* , 2000, The Journal of Biological Chemistry.

[47]  R. Swerlick,et al.  Identification and Characterization of a Novel Cytokine-inducible Nuclear Protein from Human Endothelial Cells (*) , 1995, The Journal of Biological Chemistry.

[48]  D. Botstein,et al.  Cluster analysis and display of genome-wide expression patterns. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[49]  D. Pette,et al.  Changes in FGF and FGF receptor expression in low-frequency-stimulated rat muscles and rat satellite cell cultures. , 1999, Differentiation; research in biological diversity.

[50]  J. Fluckey,et al.  Attenuated insulin action on glucose uptake and transport in muscle following resistance exercise in rats. , 1999, Acta physiologica Scandinavica.

[51]  E. Richter,et al.  Eccentric exercise decreases glucose transporter GLUT4 protein in human skeletal muscle. , 1995, The Journal of physiology.

[52]  E. Richter,et al.  Eccentric exercise decreases maximal insulin action in humans: muscle and systemic effects. , 1996, The Journal of physiology.

[53]  Steven C. Lawlor,et al.  MAPPFinder: using Gene Ontology and GenMAPP to create a global gene-expression profile from microarray data , 2003, Genome Biology.