Attaix D, Taillandier D, Temparis S, Larbaud D, Aurousseau E, Combaret L, Voisin L
INRA-Theix, Centre de Recherche en Nutrition Humaine de Clermont-Ferrand, Saint Genès-Champanelle, France.
Reprod Nutr Dev. 1994;34(6):583-97. doi: 10.1051/rnd:19940605.
Protein breakdown plays a major role in muscle growth and atrophy. However, the regulation of muscle proteolysis by nutritional, hormonal and mechanical factors remains poorly understood. In this review, the methods available to study skeletal muscle protein breakdown, and our current understanding of the role of 3 major proteolytic systems that are well characterized in this tissue (ie the lysosomal, Ca(2+)-dependent and ATP-ubiquitin-dependent proteolytic pathways) are critically analyzed. ATP-ubiquitin-dependent proteolysis is discussed in particular since recent data strongly suggest that this pathway may be responsible for the loss of myofibrillar proteins in many muscle-wasting conditions in rodents. In striking contrast to either the lysosomal or the Ca(2+)-dependent processes, ATP-ubiquitin-dependent protein breakdown is systematically influenced by nutritional manipulation (fasting and dietary protein deficiency), muscle activity and disuse (denervation atrophy and simulated weightlessness), as well as pathological conditions (sepsis, cancer, trauma and acidosis). The hormonal control of this pathway, its possible substrates, rate-limiting step, and functional associations with other proteolytic systems are discussed.
蛋白质分解代谢在肌肉生长和萎缩过程中起着重要作用。然而，营养、激素和机械因素对肌肉蛋白水解的调节作用仍知之甚少。在这篇综述中，我们对目前用于研究骨骼肌蛋白质分解代谢的方法，以及对该组织中3种主要蛋白水解系统（即溶酶体、钙依赖和ATP-泛素依赖的蛋白水解途径）作用的当前认识进行了批判性分析。特别讨论了ATP-泛素依赖的蛋白水解作用，因为最近的数据有力地表明，该途径可能是啮齿动物许多肌肉萎缩情况下肌原纤维蛋白丢失的原因。与溶酶体或钙依赖过程形成鲜明对比的是，ATP-泛素依赖的蛋白质分解受到营养操纵（禁食和膳食蛋白质缺乏）、肌肉活动和废用（去神经萎缩和模拟失重）以及病理状况（脓毒症、癌症、创伤和酸中毒）的系统性影响。本文还讨论了该途径的激素控制、可能的底物、限速步骤以及与其他蛋白水解系统的功能关联。
