Pulmonology Department, IMIM-Hospital del Mar, Catalonia, Spain .
Antioxid Redox Signal. 2010 Mar;12(3):417-29. doi: 10.1089/ars.2009.2808.
Relatively low levels of reactive oxygen species (ROS) produced inside resting skeletal muscles play important functions in cell signaling. When ROS production increases to levels beyond the buffering capacity of muscle antioxidant systems, a state of oxidative stress develops, which leads to skeletal muscle contractile dysfunction. A clear association between oxidative stress and depressed skeletal muscle performance has been described in several acute and chronic conditions, such as systemic inflammation and chronic obstructive lung diseases. The observation that the levels of oxidant-derived posttranslational protein modifications, including protein carbonylation, are elevated inside skeletal muscle fibers when oxidative stress develops suggest that these modifications play important roles in regulating muscle function. This proposal is supported by recent studies that unveiled that several myofilament (myosin heavy chain and actin), mitochondrial (aconitase, creatine kinase), and cytosolic (enolase, aldolase and glyceraldehyde 3-phosphate dehydrogenase and carbonic anhydrase III) proteins are carbonylated inside skeletal muscle fibers in many animal models of muscle dysfunction, and in humans with impaired skeletal muscle contractility. However, the functional importance of carbonylation in determining the function of muscle-specific proteins and the precise contribution of carbonylation-induced dysfunction of these proteins to overall muscle contractile deficit in various pathologies remain to be determined.
在休息状态下的骨骼肌内产生的相对低水平的活性氧（ROS）在细胞信号转导中发挥重要功能。当 ROS 的产生增加到超过肌肉抗氧化系统的缓冲能力的水平时，就会发生氧化应激状态，导致骨骼肌收缩功能障碍。在几种急性和慢性疾病中，如全身炎症和慢性阻塞性肺疾病，已经描述了氧化应激与骨骼肌性能下降之间的明确关联。当氧化应激发生时，观察到氧化应激衍生的翻译后蛋白修饰（包括蛋白羰基化）水平在骨骼肌纤维内升高，这表明这些修饰在调节肌肉功能方面发挥着重要作用。这一观点得到了最近的研究支持，这些研究揭示了在许多肌肉功能障碍的动物模型以及骨骼肌收缩力受损的人类中，几种肌丝（肌球蛋白重链和肌动蛋白）、线粒体（乌头酸酶、肌酸激酶）和细胞质（烯醇酶、醛缩酶和甘油醛-3-磷酸脱氢酶和碳酸酐酶 III）蛋白在内的骨骼肌纤维内发生了羰基化。然而，羰基化在确定肌肉特异性蛋白功能中的作用以及这些蛋白的羰基化诱导功能障碍对各种病理状态下整体肌肉收缩缺陷的精确贡献仍有待确定。
