Trenerry Marissa K, Carey Kate A, Ward Alister C, Farnfield Michelle M, Cameron-Smith David
School of Exercise and Nutrition Science, Deakin University, 221 Burwood Highway, Burwood, Victoria 3125, Australia.
Rejuvenation Res. 2008 Aug;11(4):717-24. doi: 10.1089/rej.2007.0643.
Activation of the transcription factor signal transducers and activators of transcription (STAT) 3 is common to many inflammatory cytokines and growth factors, with recent evidence of involvement in skeletal muscle regeneration. The purpose of this study was to determine whether STAT3 signaling activation is regulated differentially, at rest and following intense resistance exercise, in aged human skeletal muscle. Skeletal muscle biopsies were harvested from healthy younger (n = 11, 20.4 +/- 0.8 years) and older men (n = 10, 67.4 +/- 1.3 years) under resting conditions and 2 h after the completion of resistance exercise. No differences were evident at rest, whereas the phosphorylation of STAT3 was significantly increased in old (23-fold) compared to young (5-fold) subjects after exercise. This correlated with significantly higher induction of the STAT3 target genes including; interleukin-6 (IL-6), JUNB, c-MYC, and suppressor of cytokine signaling (SOCS) 3 mRNA in older subjects following exercise. Despite increased SOCS3 mRNA, cellular protein abundance was suppressed. SOCS3 protein is an important negative regulator of STAT3 activation and cytokine signaling. Thus, in aged human muscle, elevated responsiveness of the STAT3 signaling pathway and suppressed SOCS3 protein are evident following resistance exercise. These data suggest that enhanced STAT3 signaling responsiveness to proinflammatory factors may impact on mechanisms of muscle repair and regeneration.
转录因子信号转导子与转录激活子（STAT）3的激活在许多炎性细胞因子和生长因子中都很常见，最近有证据表明其参与骨骼肌再生。本研究的目的是确定在老年人类骨骼肌中，STAT3信号激活在静息状态和剧烈抗阻运动后是否受到不同调节。在静息状态下以及抗阻运动结束后2小时，从健康的年轻男性（n = 11，20.4 +/- 0.8岁）和老年男性（n = 10，67.4 +/- 1.3岁）获取骨骼肌活检样本。静息时未发现明显差异，而运动后老年受试者（23倍）相比年轻受试者（5倍），STAT3的磷酸化显著增加。这与老年受试者运动后STAT3靶基因包括白细胞介素-6（IL-6）、JUNB、c-MYC和细胞因子信号抑制因子（SOCS）3 mRNA的显著更高诱导相关。尽管SOCS3 mRNA增加，但细胞蛋白丰度受到抑制。SOCS3蛋白是STAT3激活和细胞因子信号的重要负调节因子。因此，在老年人类肌肉中，抗阻运动后STAT3信号通路的反应性增强和SOCS3蛋白受到抑制是明显的。这些数据表明，STAT3信号对促炎因子的反应性增强可能会影响肌肉修复和再生机制。
