Reid Michael B, Durham William J
Department of Medicine, Baylor College of Medicine, One Baylor Plaza, Houston, Texas 77030, USA.
Ann N Y Acad Sci. 2002 Apr;959:108-16. doi: 10.1111/j.1749-6632.2002.tb02087.x.
Since the early 1980s biologists have recognized that skeletal muscle generates free radicals. Of particular interest are two closely related redox cascades--reactive oxygen species (ROS) and nitric oxide (NO) derivatives. The ROS cascade is initiated by superoxide anion radicals derived from the mitochondrial electron transport chain, the membrane-associated NAD(P)H oxidase complex, or other sources. NO is produced by two NO synthase isoforms constitutively expressed by muscle fibers. ROS and NO derivatives are produced continually and are detectable in both the cytosolic and extracellular compartments. Production increases during strenuous exercise. Both ROS and NO modulate contractile function. Under basal conditions, low levels of ROS enhance force production. Excessive ROS accumulation inhibits force, for example, during fatiguing exercise. NO inhibits skeletal muscle contraction, an effect that is partially mediated by cyclic GMP as a second messenger. With aging, redox modulation of muscle contraction may be altered by changes in the rates of ROS and NO production, the levels of endogenous antioxidants that buffer ROS and NO, and the sensitivities of regulatory proteins to ROS and NO action. The impact of aging on contractile regulation depends on the relative magnitude of these changes and their net effects on ROS and NO activities at the cellular level.
自20世纪80年代初以来，生物学家已经认识到骨骼肌会产生自由基。特别令人感兴趣的是两个密切相关的氧化还原级联反应——活性氧（ROS）和一氧化氮（NO）衍生物。ROS级联反应由线粒体电子传递链、膜相关的NAD(P)H氧化酶复合物或其他来源产生的超氧阴离子自由基引发。NO由肌肉纤维组成性表达的两种NO合酶亚型产生。ROS和NO衍生物持续产生，在细胞溶质和细胞外区室中均可检测到。在剧烈运动期间产生会增加。ROS和NO都调节收缩功能。在基础条件下，低水平的ROS会增强力量产生。过量的ROS积累会抑制力量，例如在疲劳运动期间。NO抑制骨骼肌收缩，这种作用部分由环鸟苷酸作为第二信使介导。随着年龄的增长，肌肉收缩的氧化还原调节可能会因ROS和NO产生速率的变化、缓冲ROS和NO的内源性抗氧化剂水平以及调节蛋白对ROS和NO作用的敏感性的变化而改变。衰老对收缩调节的影响取决于这些变化的相对大小及其在细胞水平上对ROS和NO活性的净效应。
