Bhat Anjali, Abu Rafay, Jagadesan Sankarasubramanian, Vellichirammal Neetha Nanoth, Pendyala Ved Vasishtha, Yu Li, Rudebush Tara L, Guda Chittibabu, Zucker Irving H, Kumar Vikas, Gao Lie
Department of Anesthesiology, University of Nebraska Medical Center, Omaha, NE 68198, USA.
Mass Spectrometry and Proteomics Core Facility, University of Nebraska Medical Center, Omaha, NE 68198, USA.
Antioxidants (Basel). 2023 Jan 9;12(1):151. doi: 10.3390/antiox12010151.
Exercise training (ExT) improves skeletal muscle health via multiple adaptative pathways. Nrf2 is a principal antioxidant transcription factor responsible for maintaining intracellular redox homeostasis. In this study, we hypothesized that Nrf2 is essential for adaptative responses to ExT and thus beneficial for muscle. Experiments were carried out on male wild type (WT) and iMS- inducible muscle-specific Nrf2 (KO) mice, which were randomly assigned to serve as sedentary controls (Sed) or underwent 3 weeks of treadmill ExT thus generating four groups: WT-Sed, WT-ExT, KO-Sed, and KO-ExT groups. Mice were examined for exercise performance and in situ tibialis anterior (TA) contractility, followed by mass spectrometry-based proteomics and bioinformatics to identify differentially expressed proteins and signaling pathways. We found that maximal running distance was significantly longer in the WT-ExT group compared to the WT-Sed group, whereas this capacity was impaired in KO-ExT mice. Force generation and fatigue tolerance of the TA were enhanced in WT-ExT, but reduced in KO-ExT, compared to Sed controls. Proteomic analysis further revealed that ExT upregulated 576 proteins in WT but downregulated 207 proteins in KO mice. These proteins represent pathways in redox homeostasis, mitochondrial respiration, and proteomic adaptation of muscle to ExT. In summary, our data suggest a critical role of Nrf2 in the beneficial effects of SkM and adaptation to ExT.
运动训练（ExT）通过多种适应性途径改善骨骼肌健康。Nrf2是一种主要的抗氧化转录因子，负责维持细胞内的氧化还原稳态。在本研究中，我们假设Nrf2对于ExT的适应性反应至关重要，因此对肌肉有益。实验在雄性野生型（WT）和iMS-诱导型肌肉特异性Nrf2（KO）小鼠上进行，这些小鼠被随机分配作为久坐对照组（Sed）或进行3周的跑步机ExT，从而产生四组：WT-Sed、WT-ExT、KO-Sed和KO-ExT组。检测小鼠的运动能力和原位胫前肌（TA）收缩力，随后进行基于质谱的蛋白质组学和生物信息学分析，以鉴定差异表达的蛋白质和信号通路。我们发现，与WT-Sed组相比，WT-ExT组的最大跑步距离显著更长，而KO-ExT小鼠的这种能力受损。与Sed对照组相比，WT-ExT组TA的力产生和疲劳耐受性增强，但KO-ExT组降低。蛋白质组学分析进一步显示，ExT使WT小鼠中576种蛋白质上调，但在KO小鼠中使207种蛋白质下调。这些蛋白质代表了氧化还原稳态、线粒体呼吸以及肌肉对ExT的蛋白质组适应性中的途径。总之，我们的数据表明Nrf2在骨骼肌有益作用和对ExT的适应性中起关键作用。
