Skeletal muscle preservation is a dynamic process that involves constant repair and regeneration. However, the regenerative capacity of muscle cells declines in hyperglycemia. This study aimed to explore the molecular mechanisms underlying this glucotoxicity during myoblast differentiation. C2C12 cells were exposed to different concentrations of glucose, to recapitulate the development of skeletal muscles in vivo in normo- and hyperglycemic conditions. In high glucose conditions, we found significant increases in levels of total cellular reactive oxygen species (ROS) and a reorganization of SUMO enzyme transcripts and SUMOylated proteins. Furthermore, in anticipation of the ROS-induced damage to newly formed myotubes, we observed acceleration of myogenesis. Interestingly, we found a tight relationship between SUMOylation of the Histone methyltransferase SET7/9 and the maintenance of sarcomeric structures of newly formed myotubes. Finally, treatment with the antioxidant anacardic acid preserved the function and activity of myotubes generated in high-glucose conditions by interfering with both ROS and SUMO pathways. Combined, these results suggest that increased oxidative stress and modulation of SUMO reactions are key mediators of glucotoxicity and inhibition of these perturbations using antioxidants might improve muscle regeneration in hyperglycemia.

骨骼肌保存是一个动态过程，涉及不断的修复和再生。然而，高血糖症中肌肉细胞的再生能力下降。这项研究旨在探讨成肌细胞分化过程中这种糖毒性的分子机制。将C2C12细胞暴露于不同浓度的葡萄糖，以概括体内在正常血糖和高血糖情况下骨骼肌的发育。在高葡萄糖条件下，我们发现总细胞活性氧（ROS）的水平显着增加，并且SUMO酶转录物和SUMO酰化蛋白发生了重组。此外，在预期ROS引起的对新形成的肌管的损害中，我们观察到了肌发生的加速。有趣的是 我们发现组蛋白甲基转移酶SET7 / 9的SUMOylation与新形成的肌管的肌节结构的维持之间存在紧密的关系。最后，抗氧化剂漆树酸处理通过干扰ROS和SUMO途径，保留了在高糖条件下产生的肌管的功能和活性。综合起来，这些结果表明，氧化应激的增加和SUMO反应的调节是糖毒性的关键介质，使用抗氧化剂抑制这些干扰可能会改善高血糖症的肌肉再生。抗氧化剂漆树酸的治疗通过干扰ROS和SUMO途径，保留了在高糖条件下产生的肌管的功能和活性。综合起来，这些结果表明，氧化应激的增加和SUMO反应的调节是糖毒性的关键介质，使用抗氧化剂抑制这些干扰可能会改善高血糖症的肌肉再生。用抗氧化剂无烟果酸处理可通过干扰ROS和SUMO途径来保留在高糖条件下产生的肌管的功能和活性。综合起来，这些结果表明，氧化应激的增加和SUMO反应的调节是糖毒性的关键介质，使用抗氧化剂抑制这些干扰可能会改善高血糖症的肌肉再生。