title: Transcriptional regulation of gene expression in human skeletal muscle during recovery from exercise.
abstract: Exercise training elicits a number of adaptive changes in skeletal muscle that result in an improved metabolic efficiency. The molecular mechanisms mediating the cellular adaptations to exercise training in human skeletal muscle are unknown. To test the hypothesis that recovery from exercise is associated with transcriptional activation of specific genes, six untrained male subjects completed 60-90 min of exhaustive one-legged knee extensor exercise for five consecutive days. On day 5, nuclei were isolated from biopsies of the vastus lateralis muscle of the untrained and the trained leg before exercise and from the trained leg immediately after exercise and after 15 min, 1 h, 2 h, and 4 h of recovery. Transcriptional activity of the uncoupling protein 3 (UCP3), pyruvate dehydrogenase kinase 4 (PDK4), and heme oxygenase-1 (HO-1) genes (relative to beta-actin) increased by three- to sevenfold in response to exercise, peaking after 1-2 h of recovery. Increases in mRNA levels followed changes in transcription, peaking between 2 and 4 h after exercise. Lipoprotein lipase and carnitine pamitoyltransferase I gene transcription and mRNA levels showed similar but less dramatic induction patterns, with increases ranging from two- to threefold. In a separate study, a single 4-h bout of cycling exercise (n = 4) elicited from 5 to >20-fold increases in UCP3, PDK4, and HO-1 transcription, suggesting that activation of these genes may be related to the duration or intensity of exercise. These data demonstrate that exercise induces transient increases in transcription of metabolic genes in human skeletal muscle. Moreover, the findings suggest that the cumulative effects of transient increases in transcription during recovery from consecutive bouts of exercise may represent the underlying kinetic basis for the cellular adaptations associated with exercise training.
authors.affiliation: Copenhagen Muscle Research Centre, The August Krogh Institute, University of Copenhagen, DK-2100 Copenhagen, Denmark.
authors.forename: H
authors.initials: H
authors.lastname: Pilegaard
authors.forename: G A
authors.initials: GA
authors.lastname: Ordway
authors.forename: B
authors.initials: B
authors.lastname: Saltin
authors.forename: P D
authors.initials: PD
authors.lastname: Neufer
mesh_terms: D000199:Actins / Q000235:genetics / Q000378:metabolism; D000328:Adult; D002334:Carnitine O-Palmitoyltransferase / Q000235:genetics / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D005080:Exercise Test; D005786:Gene Expression Regulation / Q000502:physiology*; D006006:Glycogen Synthase / Q000235:genetics / Q000378:metabolism; D006419:Heme Oxygenase (Decyclizing) / Q000235:genetics / Q000378:metabolism; D051547:Heme Oxygenase-1; D006593:Hexokinase / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007473:Ion Channels; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D007866:Leg / Q000502:physiology; D008071:Lipoprotein Lipase / Q000235:genetics / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D018482:Muscle, Skeletal / Q000378:metabolism*; D005082:Physical Exertion / Q000502:physiology*; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D012146:Rest / Q000502:physiology*; D014158:Transcription, Genetic / Q000502:physiology*; D000071247:Uncoupling Protein 3
chemical_list: D000199:Actins; D002352:Carrier Proteins; D007473:Ion Channels; D007527:Isoenzymes; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D012333:RNA, Messenger; C000604392:UCP3 protein, human; D000071247:Uncoupling Protein 3; C496541:HMOX1 protein, human; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1; D002334:Carnitine O-Palmitoyltransferase; D006006:Glycogen Synthase; D011494:Protein Kinases; C403287:pyruvate dehydrogenase kinase 4; D006593:Hexokinase; D008071:Lipoprotein Lipase