title: Exercise alters mRNA expression of telomere-repeat binding factor 1 in skeletal muscle via p38 MAPK.
abstract: Telomeres protect chromosome ends and shorten with age in most tissues. Integral to the maintenance of telomeres is the protein complex shelterin. The gene expression regulation of shelterin proteins to physiological stressors is not understood in vivo. We have recently reported increased telomere-repeat binding factor 1 (TRF1) protein expression and longer telomere length in skeletal muscle of sedentary compared with chronically active mice. These provocative observations led us to examine the effects of acute physiological stress on shelterin expression in vivo in mice and to further define potential mechanisms associated with gene regulation of shelterin. Three groups of female C57Bl/6 mice were studied: one control group and two groups that underwent a 30-min treadmill running bout and were killed either immediately following or 1-h after the exercise. Following the exercise bout, mRNA expression of Trf1 was significantly reduced in the plantaris muscle, and this reduction was paralleled by significant increases in p38 MAPK phosphorylation. To determine if p38 mediated the decreases in Trf1 mRNA expression, C2C12 myotubes were treated with the calcium ionophore, A23187. In response to the A23187, Trf1 gene expression was significantly reduced, coupled with significant increases in p38 phosphorylation, similar to in vivo data. C2C12 myotubes pretreated with a p38 inhibitor (SB-202190) prevented the A23187-induced decrease in Trf1 mRNA expression, indicating a link between Trf1 gene expression and p38 MAPK activation. While it is too early to definitively report the effect of exercise on telomere biology in rodents or humans, these data provide important mechanistic insights into the paradoxical telomere shortening that occurs in skeletal muscle in response to chronic exercise in mice.
authors.affiliation: Department of Kinesiology, School of Public Health, University of Maryland at College Park, College Park, Maryland 20742, USA.
authors.forename: Andrew T
authors.initials: AT
authors.lastname: Ludlow
authors.forename: Laila C J
authors.initials: LC
authors.lastname: Lima
authors.forename: Jenny
authors.initials: J
authors.lastname: Wang
authors.forename: Erik D
authors.initials: ED
authors.lastname: Hanson
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Guth
authors.forename: Espen E
authors.initials: EE
authors.lastname: Spangenburg
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Roth
mesh_terms: D000818:Animals; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D061207:Calcium Ionophores / Q000494:pharmacology; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D015536:Down-Regulation; D004789:Enzyme Activation; D005260:Female; D020935:MAP Kinase Signaling System; D051379:Mice; D008810:Mice, Inbred C57BL; D009119:Muscle Contraction; D018485:Muscle Fibers, Skeletal / Q000187:drug effects / Q000201:enzymology; D018482:Muscle, Skeletal / Q000187:drug effects / Q000201:enzymology*; D010766:Phosphorylation; D005082:Physical Exertion; D012333:RNA, Messenger / Q000378:metabolism*; D000089804:Shelterin Complex; D034501:Telomere-Binding Proteins; D035321:Telomeric Repeat Binding Protein 1 / Q000235:genetics* / Q000378:metabolism; D035341:Telomeric Repeat Binding Protein 2 / Q000235:genetics / Q000378:metabolism; D013997:Time Factors; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: D061207:Calcium Ionophores; D004268:DNA-Binding Proteins; C507326:POT1 protein, mouse; C512707:POT1b protein, mouse; D012333:RNA, Messenger; D000089804:Shelterin Complex; C534796:TRF2 protein, mouse; D034501:Telomere-Binding Proteins; D035321:Telomeric Repeat Binding Protein 1; D035341:Telomeric Repeat Binding Protein 2; D000001:Calcimycin; D048051:p38 Mitogen-Activated Protein Kinases; D002118:Calcium