Bosutti Alessandra, Degens Hans
School of Healthcare Science, Manchester Metropolitan University, Manchester, United Kingdom.
Sci Rep. 2015 Jan 28;5:8093. doi: 10.1038/srep08093.
While reactive oxygen species (ROS) play a role in muscle repair, excessive amounts of ROS for extended periods may lead to oxidative stress. Antioxidants, as resveratrol (RS), may reduce oxidative stress, restore mitochondrial function and promote myogenesis and hypertrophy. However, RS dose-effectiveness for muscle plasticity is unclear. Therefore, we investigated RS dose-response on C2C12 myoblast and myotube plasticity 1. in the presence and 2. absence of different degrees of oxidative stress. Low RS concentration (10 μM) stimulated myoblast cell cycle arrest, migration and sprouting, which were inhibited by higher doses (40-60 μM). RS did not increase oxidative capacity. In contrast, RS induced mitochondria loss, reduced cell viability and ROS production, and activated stress response pathways [Hsp70 and pSer36-p66(ShcA) proteins]. However, the deleterious effects of H2O2 (1000 µM) on cell migration were alleviated after preconditioning with 10 µM-RS. This dose also enhanced cell motility mediated by 100 µM-H2O2, while higher RS-doses augmented the H2O2-induced impaired myoblast regeneration and mitochondrial dehydrogenase activity. In conclusion, low resveratrol doses promoted in vitro muscle regeneration and attenuated the impact of ROS, while high doses augmented the reduced plasticity and metabolism induced by oxidative stress. Thus, the effects of resveratrol depend on its dose and degree of oxidative stress.
虽然活性氧（ROS）在肌肉修复中发挥作用，但长时间过量的ROS可能导致氧化应激。抗氧化剂，如白藜芦醇（RS），可能会降低氧化应激，恢复线粒体功能，并促进肌生成和肥大。然而，RS对肌肉可塑性的剂量有效性尚不清楚。因此，我们研究了RS对C2C12成肌细胞和肌管可塑性的剂量反应：1. 在存在和2. 不存在不同程度氧化应激的情况下。低RS浓度（10μM）刺激成肌细胞周期停滞、迁移和发芽，而高剂量（40 - 60μM）则抑制这些过程。RS并未增加氧化能力。相反，RS导致线粒体丢失，降低细胞活力和ROS产生，并激活应激反应途径[Hsp70和pSer36 - p66(ShcA)蛋白]。然而，在用10μM - RS预处理后，H2O2（1000μM）对细胞迁移的有害影响得到缓解。该剂量还增强了由100μM - H2O2介导的细胞运动性，而较高的RS剂量则加剧了H2O2诱导的成肌细胞再生受损和线粒体脱氢酶活性。总之，低剂量白藜芦醇促进体外肌肉再生并减轻ROS的影响，而高剂量则加剧氧化应激诱导的可塑性和代谢降低。因此，白藜芦醇的作用取决于其剂量和氧化应激程度。
