Sepsis: Stimulation of energy-dependent protein breakdown resulting in protein loss in skeletal muscle
Sepsis: Stimulation of energy-dependent protein breakdown resulting in protein loss in skeletal muscle
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DOI：
10.1007/s002689900370
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发表时间：
1998-02-01
影响因子：
2.6
通讯作者：
Fischer, JE
中科院分区：
文献类型：
--
作者：
Hasselgren, PO;Fischer, JE
肌肉紧张症是败血症、严重感染和损伤的特征性代谢反应。在严重和长期脓毒症患者中，分解代谢反应导致肌肉萎缩和疲劳，这可能对这些患者的结局产生不利影响。从临床角度来看，了解脓毒症期间肌肉蛋白质分解的调节及其机制非常重要，对于开发新的治疗方法以防止肌肉组织蛋白质丢失至关重要。在脓毒症患者和实验动物中的研究提供了证据，证明肌原纤维蛋白肌动蛋白和肌球蛋白对脓毒症的影响特别敏感。在脓毒症期间调节肌肉蛋白质分解的因素中，促炎细胞因子肿瘤坏死因子和白细胞介素-1以及糖皮质激素是主要介质。细胞内蛋白质分解受多种蛋白水解途径调节。其中，能量-泛素依赖性途径占脓毒症期间肌肉蛋白质分解的主要部分。特异性蛋白酶体抑制剂的开发可能使其在未来有可能靶向脓毒症诱导的肌肉蛋白水解增加的分子机制。这种治疗可能被证明是减少严重感染或脓毒症患者代谢成本的重要途径。
Muscle catabolism is a characteristic metabolic response to sepsis, severe infection, and injury. In patients with severe and protracted sepsis, the catabolic response results in muscle wasting and fatigue, which may adversely affect the outcome in these patients. An understanding of the regulation of muscle protein breakdown during sepsis and the mechanisms involved is important from a clinical standpoint and is essential for the development of new therapeutic modalities to prevent protein loss from muscle tissue. Studies in septic patients and experimental animals have provided evidence that the myofibrillar proteins actin and myosin are particularly sensitive to the effects of sepsis. Among the factors that regulate muscle protein breakdown during sepsis, the proinflammatory cytokines tumor necrosis factor and interleukin-1, together with glucocorticoids, are the principal mediators. Intracellular protein breakdown is regulated by multiple proteolytic pathways. Among these, the energy-ubiquitin-dependent pathway accounts for a major portion of muscle protein breakdown during sepsis. The development of specific proteasome inhibitors may make it possible in the future to target the molecular mechanisms of sepsis-induced increase in muscle proteolysis. Such treatment may prove an important avenue to reduce the metabolic cost in patients with severe infection or sepsis.