title: The unfolded protein response is triggered following a single, unaccustomed resistance-exercise bout.
abstract: Endoplasmic reticulum (ER) stress results from an imbalance between the abundance of synthesized proteins and the folding capacity of the ER. In response, the unfolded protein response (UPR) attempts to restore ER function by attenuating protein synthesis and inducing chaperone expression. Resistance exercise (RE) stimulates protein synthesis; however, a postexercise accumulation of unfolded proteins may activate the UPR. Aging may impair protein folding, and the accumulation of oxidized and misfolded proteins may stimulate the UPR at rest in aged muscle. Eighteen younger (n = 9; 21 ± 3 yr) and older (n = 9; 70 ± 4 yr) untrained men completed a single, unilateral bout of RE using the knee extensors (four sets of 10 repetitions at 75% of one repetition maximum on the leg press and leg extension) to determine whether the UPR is increased in resting, aged muscle and whether RE stimulates the UPR. Muscle biopsies were taken from the nonexercised and exercised vastus lateralis at 3, 24, and 48 h postexercise. Age did not affect any of the proteins and transcripts related to the UPR. Glucose-regulated protein 78 (GRP78) and protein kinase R-like ER protein kinase (PERK) proteins were increased at 48 h postexercise, whereas inositol-requiring enzyme 1 alpha (IRE1α) was elevated at 24 h and 48 h. Despite elevated protein, GRP78 and PERK mRNA was unchanged; however, IRE1α mRNA was increased at 24 h postexercise. Activating transcription factor 6 (ATF6) mRNA increased at 24 h and 48 h, whereas ATF4, CCAAT/enhancer-binding protein homologous protein (CHOP), and growth arrest and DNA damage protein 34 mRNA were unchanged. These data suggest that RE activates specific pathways of the UPR (ATF6/IRE1α), whereas PERK/eukaryotic initiation factor 2 alpha/CHOP does not. In conclusion, acute RE results in UPR activation, irrespective of age.
authors.affiliation: Department of Medical Sciences, McMaster University, Hamilton, Ontario, Canada;
authors.forename: Daniel I
authors.initials: DI
authors.lastname: Ogborn
authors.affiliation: Department of Kinesiology, McMaster University, Hamilton, Ontario, Canada; and.
authors.forename: Bryon R
authors.initials: BR
authors.lastname: McKay
authors.affiliation: Department of Kinesiology, McMaster University, Hamilton, Ontario, Canada; and.
authors.forename: Justin D
authors.initials: JD
authors.lastname: Crane
authors.affiliation: Department of Kinesiology, McMaster University, Hamilton, Ontario, Canada; and.
authors.forename: Gianni
authors.initials: G
authors.lastname: Parise
authors.affiliation: Department of Pediatrics and Medicine, McMaster University, Hamilton, Ontario, Canada tarnopol@mcmaster.ca.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Tarnopolsky
mesh_terms: D051701:Activating Transcription Factor 4 / Q000235:genetics / Q000378:metabolism; D051702:Activating Transcription Factor 6 / Q000235:genetics / Q000378:metabolism; D000293:Adolescent; D000367:Age Factors; D000368:Aged; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D000091342:Endoplasmic Reticulum Chaperone BiP; D059865:Endoplasmic Reticulum Stress; D004722:Endoribonucleases / Q000235:genetics / Q000378:metabolism; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008297:Male; D009119:Muscle Contraction; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D052097:Quadriceps Muscle / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D055070:Resistance Training; D015398:Signal Transduction; D013997:Time Factors; D051742:Transcription Factor CHOP / Q000235:genetics / Q000378:metabolism; D056811:Unfolded Protein Response; D055815:Young Adult; D019892:eIF-2 Kinase / Q000235:genetics / Q000378:metabolism
chemical_list: C497109:ATF4 protein, human; C497111:ATF6 protein, human; D051702:Activating Transcription Factor 6; C497249:DDIT3 protein, human; D000091342:Endoplasmic Reticulum Chaperone BiP; C000717247:HSPA5 protein, human; D006360:Heat-Shock Proteins; D012333:RNA, Messenger; D051701:Activating Transcription Factor 4; D051742:Transcription Factor CHOP; C460640:EIF2AK3 protein, human; C528229:ERN1 protein, human; D017346:Protein Serine-Threonine Kinases; D019892:eIF-2 Kinase; D004722:Endoribonucleases
keywords: aging; endoplasmic reticulum; resistance exercise; skeletal muscle; unfolded protein response