Department of Medical Sciences, McMaster University, Hamilton, Ontario, Canada;
Department of Kinesiology, McMaster University, Hamilton, Ontario, Canada; and.
Am J Physiol Regul Integr Comp Physiol. 2014 Sep 15;307(6):R664-9. doi: 10.1152/ajpregu.00511.2013. Epub 2014 Jul 9.
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.
内质网（ER）应激是由于合成蛋白的丰度与 ER 的折叠能力之间失衡而引起的。作为响应，未折叠蛋白反应（UPR）试图通过减弱蛋白质合成和诱导伴侣蛋白表达来恢复 ER 功能。阻力运动（RE）刺激蛋白质合成；然而，运动后未折叠蛋白的积累可能会激活 UPR。衰老可能会损害蛋白质折叠，而氧化和错误折叠蛋白的积累可能会在静息状态下刺激衰老肌肉中的 UPR。18 名年轻（n=9；21±3 岁）和年老（n=9；70±4 岁）未经训练的男性使用膝关节伸展器（腿举和腿伸展器上 1 次最大重复次数的 75%进行 4 组 10 次重复）进行单次单侧 RE，以确定 UPR 是否在静息状态下的衰老肌肉中增加，以及 RE 是否刺激 UPR。在运动后 3、24 和 48 小时，从未运动和运动的股外侧肌中取出肌肉活检。年龄不影响与 UPR 相关的任何蛋白质和转录物。葡萄糖调节蛋白 78（GRP78）和蛋白激酶 R 样内质网蛋白激酶（PERK）蛋白在运动后 48 小时增加，而肌醇需求酶 1α（IRE1α）在 24 小时和 48 小时升高。尽管蛋白水平升高，但 GRP78 和 PERK mRNA 不变；然而，IRE1α mRNA 在运动后 24 小时增加。激活转录因子 6（ATF6）mRNA 在 24 小时和 48 小时增加，而 ATF4、CCAAT/增强子结合蛋白同源蛋白（CHOP）和生长停滞和 DNA 损伤蛋白 34 mRNA 不变。这些数据表明，RE 激活了 UPR 的特定途径（ATF6/IRE1α），而 PERK/真核起始因子 2α/CHOP 则没有。总之，急性 RE 导致 UPR 激活，与年龄无关。
