Heydemann Ahlke, McNally Elizabeth
Section of Cardiology, Department of Medicine, University of Chicago, 5841 S.Maryland, Chicago, IL 60637, USA.
J Clin Invest. 2009 Mar;119(3):448-50. doi: 10.1172/jci38618.
NOS is a key enzyme in the production of NO, a molecule that directly regulates vasorelaxation and blood supply. Diverse forms of muscle disease have been clinically associated with unusual fatigue after exercise. The localization of neuronal NOS (nNOS) at the plasma membrane of muscle has recently been shown to prevent muscle fatigue after exercise. In this issue of the JCI, Lai et al. show that dystrophin--the structural protein missing in individuals with Duchenne muscular dystrophy--anchors nNOS to the sarcolemma through a direct interaction with dystrophin spectrin-like repeats 16 and 17 (see the related article, doi:10.1172/JCI36612). Furthermore, in another recently reported study of mouse models of muscular dystrophy, phosphodiesterase 5A inhibitors were used to treat the downstream ischemia that is associated with nNOS mislocalization. Collectively, these findings significantly advance our understanding of exercise-induced muscle fatigue and its role in muscle disease.
一氧化氮合酶是生成一氧化氮的关键酶，一氧化氮是一种直接调节血管舒张和血液供应的分子。多种形式的肌肉疾病在临床上都与运动后异常疲劳有关。最近有研究表明，神经元型一氧化氮合酶（nNOS）在肌肉质膜上的定位可预防运动后的肌肉疲劳。在本期《临床研究杂志》中，赖等人表明，肌营养不良蛋白（杜兴氏肌营养不良症患者所缺失的结构蛋白）通过与肌营养不良蛋白血影蛋白样重复序列16和17直接相互作用，将nNOS锚定在肌膜上（见相关文章，doi:10.1172/JCI36612）。此外，在最近另一项关于肌肉营养不良小鼠模型的研究中，磷酸二酯酶5A抑制剂被用于治疗与nNOS定位错误相关的下游缺血。这些发现共同显著推进了我们对运动诱导的肌肉疲劳及其在肌肉疾病中作用的理解。
