腺苷酸活化蛋白激酶与骨骼肌蛋白质降解

背景：机体运动时骨骼肌收缩,ATP被大量消耗,产生大量腺苷一磷酸,导致腺苷酸活化蛋白激酶的激活。目的：综述不同运动过程中腺苷酸活化蛋白激酶活性的变化,以及腺苷酸活化蛋白激酶对骨骼肌蛋白质降解的研究成果。方法：检索中国期刊网、维普期刊数据库、www.ncbi.nlm.nih.gov/pubmed和http：//highwire.stanford.edu/网站与腺苷酸活化蛋白激酶、运动、蛋白质降解研究相关的文章。并对腺苷酸活化蛋白激酶的结构与作用,不同运动过程中腺苷酸活化蛋白激酶活性的变化,以及腺苷酸活化蛋白激酶升高对骨骼肌蛋白质降解的内容进行分析综述。结果与结论：共纳入相关文献35篇。本文综述了腺苷酸活化蛋白激酶的结构、作用的研究进展;在抗阻运动和中到大强度的周期运动中,腺苷酸活化蛋白激酶活性都可能升高,而在小强度周期运动过程中腺苷酸活化蛋白激酶活性可能不升高;腺苷酸活化蛋白激酶的活化可能对骨骼肌蛋白质的降解有促进作用。     

骨骼肌葡萄糖转运的运动性适应信号机制

运动可以使骨骼肌产生良好的生理适应.急性运动或者肌肉收缩,通过增加骨骼肌的葡萄糖摄取从而使葡萄糖保持在一个稳定的水平.急性运动引起的肌肉收缩可以引起细胞内AMP/ATP值升高,Ca2+水平的增加,蛋白激酶的激活等一系列反应.因此,可以推测急性运动引起的这些生理反应过程激活一个或者多个细胞内信号转导通路就可以增加细胞膜的葡萄糖转运蛋白4运载体活性和葡萄糖的摄取.这个复杂过程中涉及到的信号分子,如腺苷酸-活化蛋白激酶,钙离子/钙调蛋白依赖性蛋白激酶和Akt底物相对分了质量160 000蛋白.长期的运动训练可以诱导代谢基因表达的改变,引起肌纤维类型、线粒体的生物发生、葡萄精转运蛋白4水平的改变,从而调节葡萄糖的转运.运动在调节骨骼肌代谢中起着重要的生理作用,但是这些重要的生理现象的分子机制目前还不是很清楚.     

大鼠骨骼肌糖酵解限速酶在不同训练负荷过程中的变化

背景:糖酵解系统在运动时能量的消耗和利用中起重要作用,不同的训练科目的主要供能系统不同,会引起战士机体不同的适应性变化.目的:探讨不同训练负荷条件对大鼠骨骼肌相关糖酵解限速酶磷酸果糖激酶、己糖激酶和丙酮酸激酶活性的影响.方法:参照BEDFORD TG标准,建立无氧、有氧和有氧无氧交替运动大鼠跑台训练模型,并设置正常对照组.各组动物训练结束后即刻处死,应用酶偶联法检测SD大鼠骨骼肌磷酸果糖激酶、己糖激酶和丙酮酸激酶的活性.结果与结论:经过不同时间的跑台训练,无氧组大鼠骨骼肌磷酸果糖激酶活性均明显升高(P<0.05),交替运动组在训练至6周时磷酸果糖激酶活性增加(P<0.05),而有氧组磷酸果糖激酶活性在训练2周和4周后均下降(P<0.05).各组己糖激酶活性在训练4周和6周后均升高(P<0.05),其中无氧组最高(P<0.05),交替运动组己糖激酶活性高于有氧运动组(P<0.05).而无氧运动2和4周组丙酮酸激酶活性较对照组有所下降(P<0.05). 结果提示,大鼠骨骼肌糖酵解限速酶的活性不仅受运动方式的影响,而且在相同运动方式下还与训练时间的长短有关.长时间的训练,尤其是包含高速无氧训练的运动项目更能提高骨骼肌糖酵解限速酶的活性.     

运动促进2型糖尿病患者骨骼肌葡萄糖摄取机制研究进展

运动疗法是预防和治疗2型糖尿病的重要方法,运动可改善2型糖尿病患者的代谢功能。长期运动可改善线粒体功能、增加其生物标志物,增加葡萄糖转运蛋白含量。急性运动可促进含葡萄糖转运蛋白4的囊泡从骨骼肌细胞内向质膜转运,其信号通路涉及腺苷酸活化蛋白激酶的活化、一氧化氮及钙离子释放增加等。本文就运动改善2型糖尿病患者代谢功能及增加骨骼肌葡萄糖摄取机制的研究进展作一综述。     

运动对骨骼肌丝裂原活化蛋白激酶信号系统的影响

背景:丝裂原活化蛋白激酶是生物体内重要的信号转导系统之一,参与介导生长、发育、分裂、分化、死亡以及细胞间的功能同步等多种细胞过程.目的:总结丝裂原活化蛋白激酶对运动后骨骼肌适应性变化的重要作用.方法:采用计算机检索中国期刊全文数据及PubMed数据库1990-01/2009-06期间的相关文章,检索词为"运动;丝裂原活化蛋白激酶信号系统;骨骼肌;适应,Exercise;Mitogen-activated protein kinases;skeletal muscle;adaption".纳入与运动和丝裂原活化蛋白激酶信号系统研究现状与发展密切相关的文章,排除重复性研究.结果与结论:运动能够激活骨骼肌中丝裂原活化蛋白激酶信号传导系统,不同运动方式、不同类型的肌肉以及训练的时间长短都可以影响到丝裂原活化蛋白激酶的激活,而且激活后丝裂原活化蛋白激酶具有不同的时相性,丝裂原活化蛋白激酶对运动后骨骼肌的适应性变化具有重要作用.通过研究探索丝裂原活化蛋白激酶对运动后骨骼肌的适应性变化,有利于以运动相关的丝裂原活化蛋白激酶为靶点,研制和开发运动功能性食品或抗疲劳药物.     

运动诱导的骨骼肌信号机制

背景：运动可通过增强骨骼肌葡萄糖转运及胰岛素活动,来调节葡萄糖内环境。明确这些复杂过程的分子机制将无疑为治疗提供更多的靶向,也为认识这些复杂的生理过程提供最基本的知识。目的：综述运动诱导骨骼肌葡萄糖转运的分子信号机制。方法：以＂骨骼肌,运动,腺苷酸活化蛋白激酶,葡萄糖摄取,葡萄糖运载体4＂为中文检索词,以＂skeletal muscle,exercise,AMPK,glucose uptake,GLUT4＂为英文检索词。应用计算机检索PubMed数据库和中文期刊全文数据库2011年11月前发表有关运动诱导骨骼肌信号机制的研究文献,排除重复性研究及Meta分析类文章。共保留39篇文献进行综述。结果与结论：运动/收缩和胰岛素是骨骼肌葡萄糖转运的最有效的和生理相关的刺激,运动诱导的信号机制代表着糖尿病治疗药物学靶点发展的一个重要步骤。运动是通过增加骨骼肌葡萄糖摄取来改善葡萄糖内环境的,而运动诱导的葡萄糖摄取是有多种信号途径来介导的,包括腺苷酸活化蛋白激酶、非典型蛋白激酶C、钙调节依赖蛋白激酶及相对分子质量为160000的Akt底物等。这些骨骼肌信号机制通过刺激葡萄糖运载体4活动增加来调节葡萄糖的转运。     

骨骼肌收缩介导葡萄糖转运中活性氧的作用及其机制

活性氧在骨骼肌收缩介导的葡萄糖转运中扮演着十分重要的角色.但相关机制还不明确.文章综述了活性氧在骨骼肌葡萄糖转运中的作用,包括活性氧参与骨骼肌收缩介导的葡萄糖转运的适宜浓度,其机制可能涉及多种信号转导途径,如5'-一磷酸腺苷活化蛋白激酶途径、丝裂原活化蛋白激酶途径、磷脂酰肌醇3激酶/蛋白激酶B途径和Ca2+途径等.这将有助于进一步揭示运动防治胰岛素抵抗和2型糖尿病的分子机制.     

运动诱导细胞自噬在老年肌少症康复中的研究进展

老年肌少症是一种与衰老相关的疾病,由于蛋白质合成和降解两者之间的不平衡,导致骨骼肌肉的质量和强度的降低。细胞自噬作为调节体内蛋白质代谢平衡的保守机制,能够被运动诱导的腺苷酸活化蛋白激酶(AMPK)、胰岛素样生长因子(IGF)/蛋白激酶B (Akt)/哺乳动物雷帕霉素靶蛋白(mTOR)及磷脂酰肌醇3激酶(PI3K)/Akt/mTOR等多条信号通路途径调节。而运动激活的细胞自噬调控不同生理病理条件下骨骼肌重塑与内环境稳态的稳定,是骨骼肌健康维持的关键。本文总结不同运动诱导的细胞自噬在老年肌少症的预防、治疗和康复中的作用与潜在的分子机制。     

运动对大鼠骨骼肌胰岛素信号转导蛋白表达和活性的影响

目的：观察运动对大鼠骨骼肌中胰岛素信号转导蛋白表达和活性的影响，探讨运动调节骨骼肌葡萄糖转运的细胞内机制。方法：将20只SD大鼠随机分为运动组和对照组，运动组按Ploug方法进行8w的游泳训练。结果：运动组大鼠游泳8w后骨骼肌中蛋白激酶B蛋白表达和磷酸化程度均增加，细胞外信号调节激酶蛋白表达有上升趋势．磷酸化程度显著增加。结论：运动可激活正常骨骼肌中胰岛素信号传递两大途径中的关键蛋白，这可能是运动增强骨骼肌的胰岛素敏感性，促进葡萄糖转运的机制之一。     

过氧化物酶体增殖物受体γ共激活因子1与骨骼肌的适应性机制

背景:肌肉收缩活性的增加可诱导多种信号分子转录,并通过专有的信号通路激活细胞核内大量基因的表达.目的:综述过氧化物酶体增殖物受体γ共激活因子1与骨骼肌的适应机制相关方面的研究.方法:以PGC1,skeletal muscle,exercise,adaptations为检索词,检索Pubmed数据库(1995/2009-01).文献检索语种限制为英文.纳入PGC1与运动性骨骼肌适应的相关内容.排除重复性研究.以PGC1与线粒体的氧化代谢,以及运动诱导PGC1s变化与骨骼肌适应为评价指标.结果与结论:计算机初检得到57篇文献,根据纳入排除标准,对34篇进行分析.长期的耐力训练可诱导骨骼肌发生可塑性变化,包括线粒体的生物合成、肌纤维类型的改变和毛细血管密度的增加.转录因子高度依赖共激活分子从转录水平调控这些运动诱导生理性适应过程.这些转录因子的目标基因大部分涉及到线粒体的生物合成和细胞的新陈代谢,其转录调控方式可能为了解运动性能量变化特征的信号通路与线粒体生物合成及其功能之间的关系提供基本框架.提示过氧化物酶体增殖物受体γ共激活因子1α蛋白自身转录后,存在多种蛋白修饰,与多种生物学过程密切相关,可能在运动诱导骨骼肌的适应机制方面起着重要作用.     

Exercise stimulates the mitogen-activated protein kinase pathway in human skeletal muscle.

Physical exercise can cause marked alterations in the structure and function of human skeletal muscle. However, little is known about the specific signaling molecules and pathways that enable exercise to modulate cellular processes in skeletal muscle. The mitogen-activated protein kinase (MAPK) cascade is a major signaling system by which cells transduce extracellular signals into intracellular responses. We tested the hypothesis that a single bout of exercise activates the MAPK signaling pathway. Needle biopsies of vastus lateralis muscle were taken from nine subjects at rest and after 60 min of cycle ergometer exercise. In all subjects, exercise increased MAPK phosphorylation, and the activity of its downstream substrate, the p90 ribosomal S6 kinase 2. Furthermore, exercise increased the activities of the upstream regulators of MAPK, MAP kinase kinase, and Raf-1. When two additional subjects were studied using a one-legged exercise protocol, MAPK phosphorylation and p90 ribosomal S6 kinase 2, MAP kinase kinase 1, and Raf-1 activities were increased only in the exercising leg. These studies demonstrate that exercise activates the MAPK cascade in human skeletal muscle and that this stimulation is primarily a local, tissue-specific phenomenon, rather than a systemic response to exercise. These findings suggest that the MAPK pathway may modulate cellular processes that occur in skeletal muscle in response to exercise.     

Comparison of serum cardiac specific troponin-I with creatine kinase,creatine kinase-MB isoenzyme,tropomyosin, myoglobin and C-reactive protein release in marathon runners: cardiac or skeletal muscle trauma?

Problems arise in distinguishing skeletal from cardiac muscle trauma on the basis of serum enzyme tests following severe muscle exercise. The contributions of cardiac and skeletal sources have been assessed in eleven marathon runners by measuring pre- and post-race serum levels of cardiac-specific myofibrillar troponin-I together with total creatine kinase, creatine kinase-MB isoenzyme, myoglobin, myofibrillar tropomyosin and C-reactive protein. Total creatine kinase, creatine kinase-MB isoenzyme, tropomyosin and myoglobin were significantly elevated above pre-race levels in all runners between 1 h and 128 h post-race. Neither mean cardiac troponin-I nor C-reactive protein was elevated post-race. Nine out of sixty-three samples fulfilled conventional positive criteria for cardiac muscle damage on the basis of combined creatine kinase and creatine kinase-MB isoenzyme levels. Six runners had one or more positive samples. No samples had levels above twice the upper normal limit for either cardiac troponin-I or C-reactive protein. Correlation analysis of levels in each sample indicated skeletal and not cardiac muscle as the source of raised serum protein.     

运动诱导骨骼肌线粒体生成中沉默信息调节因子1的作用

背景：沉默信息调节因子 1 是新近受到体育科学领域关注的能量代谢调节因子,在运动骨骼肌线粒体生成中与其他信号分子一起发挥作用。目的：综述沉默信息调节因子 1 在运动诱导骨骼肌线粒体生物合成中的作用及机制。方法：应用计算机检索 PubMed 和 Highwire 数据库 2000 年 1 月至 2013 年 1 月有关运动、沉默信息调节因子 1、骨骼肌线粒体生物合成的文献,检索词为 SIRT1,AMPK,PGC-1α,mitochondrial biogenesis,skeletalmuscle, exercise,限定文章语言为 English。对资料进行初审,选取沉默信息调节因子 1 与运动诱导骨骼肌线粒体生物合成有关的文献,排除重复研究。结果与结论：共收集相关文献 165 篇,排除重复研究,纳入 62 篇。沉默信息调节因子 1 作为一种 NAD＋依赖的去乙酰化酶,在运动中被激活,通过上调过氧化物酶体增殖物激活受体辅激活因子表达而诱导骨骼肌线粒体生物合成,其分子机制涉及一磷酸腺苷激活的蛋白激酶、低氧诱导因子 2α等信号分子。但近年来的一些研究对沉默信息调节因子 1 在骨骼肌线粒体生物合成中的作用提出了质疑,认为其并非为运动诱导的骨骼肌线粒体生物合成所必需。沉默信息调节因子 1 在运动诱导的骨骼肌线粒体生物合成中发挥重要调控作用,但采用蛋白和活性等不同检测方法,在实验结果上可能会造成较大差异。     

Impaired actions of insulin-like growth factor 1 on protein Synthesis and degradation in skeletal muscle of rats with chronic renal failure. Evidence for a postreceptor defect.

The actions of insulin-like growth factor 1 (IGF-1) on protein turnover and of the IGF-1 receptor (IGF-1R) were examined in skeletal muscle of rats with chronic renal failure (CRF) and sham operated (SO), pair-fed controls. Acidemia was prevented in CRF rats with NaHCO3. Serum IGF-1 and skeletal muscle IGF-1 and IGF-1 mRNA were reduced in CRF rats. Dose-response studies revealed impaired stimulation of protein synthesis and suppressed inhibition of protein degradation by IGF-1 in epitrochlearis muscle of CRF rats. Neither IGF-1 analogues with low affinity to IGF binding proteins nor proteinase inhibitors obliterated the IGF-1 resistance. In CRF rats, skeletal muscle IGF-1R mRNA was increased; displacement ligand binding studies and affinity labeling of the IGF-1R alpha subunit indicated increased total skeletal muscle IGF-1R number with normal affinity. However, both autophosphorylation of the IGF-1R beta subunit (i.e., IGF-1R tyrosine kinase) and the IGF-1R tyrosine kinase activity towards exogenous insulin receptor substrate-1, a natural substrate for IGF-1R tyrosine kinase, were reduced in CRF fats. These data indicate that in skeletal muscle of CRF rats there is resistance to the IGF-1 effects on protein synthesis and degradation and decreased IGF-1 and IGF-1 mRNA levels; IGF-1R mRNA and number are increased; but activity of IGF-1R tyrosine kinase is impaired. This postreceptor defect may be a cause of the skeletal muscle resistance to IGF-1 in CRF.     

运动对慢性阻塞性肺疾病系统性炎症和骨骼肌功能障碍干预效果的系统综述

目的 系统综述运动对慢性阻塞性肺疾病(COPD)系统性炎症及骨骼肌功能障碍的干预效果。方法 检索建库至2021年6月PubMed、Web of Science、CNKI、维普和万方数据,运动对COPD系统性炎症及骨骼肌功能障碍干预效果的相关文献,并辅以参考文献回溯和手工检索。提取文献内容,对运动改善COPD系统性炎症及骨骼肌功能障碍的效果进行综述。结果 共检索到文献192篇,最终纳入8篇,245例被试。运动可以降低促炎因子水平,提高抗炎因子水平;提高COPD患者运动能力,改善骨骼肌结构。运动改善COPD系统性炎症与运动方式、强度以及持续时间有关,可能通过调控炎症反应,影响泛素-蛋白酶、胰岛素样生长因子1/磷脂酰肌醇-3-激酶/Akt等途径,改善骨骼肌功能障碍。结论 运动对降低COPD系统性炎症水平、改善骨骼肌功能障碍具有一定效果。     

The biological mechanisms of cancer-related skeletal muscle wasting: the role of progressive resistance exercise

Cancer results in perturbations in skeletal muscle protein metabolism leading to muscle wasting. Although severe wasting is seen primarily in persons with advanced malignancies, a number of cancer patients show some degree of wasting at presentation. Although cancer-related skeletal muscle wasting is attributable, in part, to decreased muscle protein synthesis, its primary cause appears to be increased muscle protein degradation. Although several proteolytic systems may be involved, compelling evidence suggests that the major system responsible for skeletal muscle protein degradation in cancer is the ATP-dependent ubiquitin- proteasome system. Other contributing factors include proinflammatory cytokines and the tumor-released proteolysis-inducing factor. Decreased physical activity and decreased nutritional intake may also play a role. Cancer-related skeletal muscle wasting is clinically significant because of its profound effects on functional outcomes and quality of life. Nevertheless, no specific interventions have proved to be effective in preventing or reversing the problem. Interventions such as nutritional supplementation and appetite stimulants are only partially helpful. A nonpharmacologic intervention that may attenuate cancer-related skeletal muscle wasting is progressive resistance exercise training (PRT). PRT is a potent stimulus of growth in muscle mass and strength. PRT may attenuate cancer-related skeletal muscle wasting by downregulating the activity of proinflammatory cytokines and by increasing the phosphorylation of intramuscular amino acid-signaling molecules. This article discusses several cancer-related skeletal muscle wasting mechanisms and proposes how PRT might attenuate muscle wasting by counteracting some of these mechanisms.     

The AMP-activated protein kinase alpha2 catalytic subunit controls whole-body insulin sensitivity

AMP-activated protein kinase (AMPK) is viewed as a fuel sensor for glucose and lipid metabolism. To better understand the physiological role of AMPK, we generated a knockout mouse model in which the AMPKalpha2 catalytic subunit gene was inactivated. AMPKalpha2(-/-) mice presented high glucose levels in the fed period and during an oral glucose challenge associated with low insulin plasma levels. However, in isolated AMPKalpha2(-/-) pancreatic islets, glucose- and L-arginine-stimulated insulin secretion were not affected. AMPKalpha2(-/-) mice have reduced insulin-stimulated whole-body glucose utilization and muscle glycogen synthesis rates assessed in vivo by the hyperinsulinemic euglycemic clamp technique. Surprisingly, both parameters were not altered in mice expressing a dominant-negative mutant of AMPK in skeletal muscle. Furthermore, glucose transport was normal in incubated isolated AMPKalpha2(-/-) muscles. These data indicate that AMPKalpha2 in tissues other than skeletal muscles regulates insulin action. Concordantly, we found an increased daily urinary catecholamine excretion in AMPKalpha2(-/-) mice, suggesting altered function of the autonomic nervous system that could explain both the impaired insulin secretion and insulin sensitivity observed in vivo. Therefore, extramuscular AMPKalpha2 catalytic subunit is important for whole-body insulin action in vivo, probably through modulation of sympathetic nervous activity.     

肌肉萎缩与过氧化体增殖活化受体γ辅助活化因子1α的关系

背景：过氧化体增殖活化受体γ辅助活化因子1α（peroxisome proliferator-activated receptorγcoactivator1α,PGC-1α）能调节骨骼肌的功能,包括有：线粒体的生物发生、底物氧化和肌纤维类型等,最近还有研究发现PGC-1α能够预防肌肉的萎缩。目的：总结并讨论PGC-1α与肌肉萎缩之间的关系。方法：由第一作者用计算机检索中国期刊全文数据库（CNKI：2000/2010）和Medline数据库（2000/2010）,关键词分别为＂肌肉萎缩,PGC-1α,运动＂和＂muscle atrophy,PGC-1α,exercise＂。共检索到56篇文章,按纳入和排除标准对文献进行筛选,共纳入22篇文章。从PGC-1α与肌肉萎缩、运动与PGC-1α共2个方面进行总结。结果与结论：PGC-1α表达增强能提高线粒体功能、人体的运动能力、降低氧化应激和抑制肌肉萎缩特异性基因的表达。说明运动可通过调节PGC-1α的表达来干预肌肉萎缩。