癌性恶液质骨骼肌蛋白降解机制  

Muscle protein breakdown in cancer cachexia

作　　者：张颖 王新颖 Zhang Ying;Wang Xinying(Department of Cardiothoracic Surgery,Jiangsu Province Hospital of Traditional Chinese Medicine,Nanjing University of Chinese Medicine,Nanjing 210029,Jiangsu,China;Department of General Surgery,General Hospital of Eastern Theater Command,Nanjing 210002,Jiangsu,China)

机构地区：[1]南京中医药大学附属医院心胸外科,南京210029 [2]东部战区总医院普通外科,南京210002

出　　处：《肿瘤代谢与营养电子杂志》2020年第3期255-258,共4页Electronic Journal of Metabolism and Nutrition of Cancer

基　　金：国家公益性行业科研专项项目(201502022);江苏省医学重点人才项目(ZDRCA2016091);国家自然科学基金项目(81470797,81770531);军事医学创新工程专项(18CXZ031)。

摘　　要：进行性的骨骼肌减少是癌性恶液质的重要特征,它与肿瘤患者术后并发症的发生率增高、放化疗的不良反应增加及生存率下降等不良预后密切相关。骨骼肌的维持有赖于骨骼肌蛋白合成和分解代谢的平衡,而骨骼肌分解增加在骨骼肌减少的机制中起到更重要的作用。泛素蛋白酶系统和自噬溶酶体系统是两种重要的细胞内蛋白质分解系统。泛素蛋白酶系统可完全或部分降解细胞中半衰期短的、变性的、异常的蛋白质。它在调节细胞信号传导和转录中具有重要功能,并参与多种细胞功能,包括细胞周期进程、细胞存活、增殖、凋亡和其他关键细胞途径。自噬主要识别和清除细胞内大的蛋白质聚集体以及功能失调或多余的细胞器,是应对各种细胞应激的关键适应机制。既往人们认为泛素蛋白酶系统和自噬溶酶体系统是两个独立的系统,然而,越来越多的研究显示两者是密切联系的功能相关的系统,它们受某些共同的信号机制调控在降解细胞内容物方面起到协同和互补作用。本文将就泛素蛋白酶系统和自噬溶酶体系统在癌性恶液质骨骼肌分解机制中的作用的相关研究进展进行综述。Muscle wasting is the central characteristic of cancer cachexia,which is associated with increased postoperative complication rates,increased susceptibility to chemotherapy toxicity,and decreased chance of survival.The muscle loss is caused by an imbalance between protein synthesis and degradation.In cancer patients,increased muscle protein breakdown seemed to play a more important role than decreased protein synthesis.The ubiquitin proteasome system(UPS)and autophagy lysosome system(ALS)are major intracellular proteolytic systems.UPS is the primary proteolytic route for short-lived,misfolded,and damaged proteins.It has important functions in the regulation of cell signaling and transcription and is involved in a variety of cellular functions,including cell cycle progression,cell survival,proliferation,apoptosis,and other critical cellular pathways.ALP recognizes and removes large and potentially dangerous cellular components such as protein aggregates and dysfunctional or superfluous organelles and has emerged as a crucial adaptive mechanism to cope with various cellular stresses.In the past,ubiquitin and the autophagy system were considered to be two independent systems.However,more and more studies show that they are closely related and functionally related systems,which serve complimentary roles in degrading cellular constituents and might be coordinately activated by common signaling mechanisms.In this review we will describe the involvement of the ubiquitin proteasome and autophagy lysosome systems in cancer cachexia that regulate tumor-induced protein breakdown in muscle.

关 键 词：肿瘤 恶液质 骨骼肌减少 自噬 泛素 

分 类 号：R730.2[医药卫生—肿瘤]