Pierce Anson P, de Waal Eric, McManus Linda M, Shireman Paula K, Chaudhuri Asish R
Sam and Ann Barshop Institute for Longevity and Aging Studies, University of Texas Health Science Center, San Antonio, TX 78229-3900, USA.
Free Radic Biol Med. 2007 Dec 15;43(12):1584-93. doi: 10.1016/j.freeradbiomed.2007.08.019. Epub 2007 Sep 4.
Molecular events that control skeletal muscle injury and regeneration are poorly understood. However, inflammation associated with oxidative stress is considered a key player in modulating this process. To understand the consequences of oxidative stress associated with muscle injury, inflammation, and regeneration, hind-limb muscles of C57Bl/6J mice were studied after injection of cardiotoxin (CT). Within 1 day post-CT injection, polymorphonuclear neutrophilic leukocyte accumulation was extensive. Compared to baseline, tissue myeloperoxidase (MPO) activity was elevated eight- and fivefold at 1 and 7 days post-CT, respectively. Ubiquitinylated protein was elevated 1 day postinjury and returned to baseline by 21 days. Cysteine residues of creatine kinase (CK) and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) were irreversibly oxidized within 1 day post-CT injection and were associated with protein conformational changes that fully recovered after 21 days. Importantly, protein structural alterations occurred in conjunction with significant decreases in CK activity at 1, 3, and 7 days post-CT injury. Interestingly, elevations in tissue MPO activity paralleled the time course of conformational changes in CK and GAPDH. In combination, these results demonstrate that muscle proteins in vivo are structurally and functionally altered via the generation of reactive oxygen species produced during inflammatory events after muscle injury and preceding muscle regeneration.
目前对控制骨骼肌损伤和再生的分子事件了解甚少。然而，与氧化应激相关的炎症被认为是调节这一过程的关键因素。为了了解与肌肉损伤、炎症和再生相关的氧化应激的后果，在给C57Bl/6J小鼠注射心脏毒素（CT）后，对其后肢肌肉进行了研究。在CT注射后1天内，多形核中性粒细胞大量积聚。与基线相比，CT注射后1天和7天，组织髓过氧化物酶（MPO）活性分别升高了8倍和5倍。泛素化蛋白在损伤后1天升高，并在21天恢复到基线水平。肌酸激酶（CK）和甘油醛-3-磷酸脱氢酶（GAPDH）的半胱氨酸残基在CT注射后1天内发生不可逆氧化，并与21天后完全恢复的蛋白质构象变化有关。重要的是，在CT损伤后1天、3天和7天，蛋白质结构改变与CK活性显著降低同时发生。有趣的是，组织MPO活性的升高与CK和GAPDH构象变化的时间进程平行。综合来看，这些结果表明，体内肌肉蛋白通过肌肉损伤后和肌肉再生前炎症事件中产生的活性氧而发生结构和功能改变。
