受体的适应性变化及细胞信号转导规律与运动的联系

背景：受体调控和转换信号并启动细胞内信号转导,使靶细胞产生生物学效应。受体调节是机体对运动适应的重要调节方式。目的：总结运动对受体的影响、受体的适应性变化及运动受体细胞信号转导规律。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）,检索词分别为＂受体,运动,适应＂和＂receptor regulation,exercise,adaption＂。共检索到137篇文章,按纳入和排除标准对文献进行筛选,共纳入37篇文章。从受体概念、受体的分类和功能,受体的功能与调节,运动对受体的影响等方面进行总结,对受体在运动中的适应性变化和调节机制等方面进行探讨。结果与结论：运动训练引起瘦素受体和胰岛素受体上调,使瘦素和胰岛素分泌发生适应性改变。适宜运动使雄激素受体结合容量和受体数量提高,长期大运动量训练和力竭使雄激素受体结合容量和受体数量下降,意味着保护细胞免受过量或长期刺激而导致生理功能紊乱。急性应激使机体各组织中糖皮质激素受体含量减少,对于防止物质代谢和能量代谢紊乱,维持机体内环境稳定有重要意义。     

创面愈合与瘦素促进的跨膜信号途径

背景:瘦素与其受体结合时,能以内分泌和旁分泌等方式促进新血管生成,调节炎症及免疫功能.目的:探讨瘦素在创面愈合中的作用及跨膜信号传导机制.方法:采用计算机检索CNKI数据库和PubMed数据库,以"瘦素,创面愈合,跨膜信号传导"和"leptin,wound healing,transmembrane singal"为关键词,语言设定为中文或英文.从瘦素在创面愈合的作用及跨膜信号传导2个方面进行总结.结果与讨论:共检索到78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.结果表明瘦素能够促进表皮角质形成细胞增殖、迁移,其跨膜信号传导涉及到JAK2,STST3,ERK1等多个信号分子.瘦素-受体信号的激活则改善创面愈合,其与瘦素促进表皮角质形成细胞增殖和再上皮化有关.     

肌肉萎缩与过氧化体增殖活化受体辅γ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 receptorγ coactivator 1α,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.     

骨骼肌卫星细胞生长因子与运动训练的关系

背景:大运动量训练可以导致骨骼肌组织微细结构的损伤性变化,而骨骼肌卫星细胞的激活、增殖与分化和肌肉组织损伤的修复有密切关系.目的:文章从训练导致肌肉组织结构性损伤需要修复的客观实际出发,提出运动后骨骼肌结构的修复与骨骼肌卫星细胞生长因子之间存在某种依赖关系.方法:由第一作者通过计算机网络检索中国期刊全文数据库(CNKI)和Medline数据库(2000/2010),检索词分别为"骨骼肌卫星细胞,生长因子,运动训练,骨骼肌超微结构"和"Skeletal muscle satellite cells,exercise,growth factor".共检索到97篇文章,按纳入和排除标准对文献进行筛选,共纳入23篇文章.从运动后骨骼肌组织修复与骨骼肌卫星细胞生长因子的激活作用机制进行总结,对两者间的联系进行分析.结果与结论:大强度训练可以导致骨骼肌组织的损伤,而卫星细胞是运动后恢复期骨骼肌修复的关键,其生长因子也与训练方式等因素有关.目前在骨骼肌卫星细胞的生长因子与运动训练之间的联系还缺乏足够的认识与研究.     

运动与机体各器官系统一氧化氮的表达

目的:就运动对机体各器官系统一氧化氮表达的影响进行阐述,为运动训练提供参考。资料来源:应用机算计检索http://www.Gssiweb.com1997-01/2003-10的文章,检索词为“exerciseQnitricoxideQnitricoxidesynthase”,限定文章语言种类为English;同时检索万方数据库1998/2003的相关文章,检索词为“运动,一氧化氮,一氧化氮合酶”,限定文章语言为中文。资料选择:纳入标准:①运动与一氧化氮的研究。②一氧化氮与机体各器官系统的研究。③运动与机体各器官系统的研究。资料提炼:共收集到89篇运动对机体器官系统一氧化氮表达影响的相关文献,其中15篇符合纳入标准,排除的74篇文章系同一类重复性研究和综述文献。资料综合:①适量的运动训练可以提高人体心血管系统的功能、调节骨骼肌的收缩、促进骨骼肌葡萄糖的吸收。②适量的运动训练还可以改善神经系统的功能;过度训练导致机体一氧化氮含量的大量增高,使机体在运动后的恢复速度减慢,甚至导致运动性疲劳等不利于运动的症状发生。结论:适量有规律的运动产生的一氧化氮一般可以改善机体各器官系统的功能,使机体对运动应激产生良好的保护作用,这些变化有利于机体运动能力的提高;过度训练引起一氧化氮产生过多,不利于机体的连续运动和运动后运动员身体功能的恢复。     

低氧训练对骨骼肌结构和功能的影响

背景:低氧训练配合运动训练来增加机体的缺氧程度,以调动体内的技能潜力,抵抗缺氧生理反应并积极适应,从而达到提高运动成绩的目的.目的:总结低氧训练对骨骼肌结构和功能的影响,为低氧训练提供理论依据和指导作用.方法:以"hypoxic training,skeletal muscle,function,structure"为检索词,检索PubMed数据库(1990/2009-03);以"低氧训练、骨骼肌、功能、结构"为检索词,检索CNKI数据库(2000/2009-05).文献检索语种限制为英文和中文.纳入低氧训练对骨骼肌结构和功能影响相关的内容,排除重复性研究.结果与结论:计算机初检得到144篇文献,根据纳入排除标准,对文献进行分析.低氧训练避免传统高原训练所引起的弊端,可以根据机体的低氧适应能力,调节低氧环境,保证正常的训练,使骨骼肌获得有益的生理适应.与单纯的低氧刺激相比,不同的低氧形式刺激和不同的训练方法结合成为不同的低氧训练模式,对骨骼肌功能和结构的影响机制更为复杂.低氧训练对骨骼肌功能和结构的影响,主要在于低氧和训练的结合形式.实验的研究对象和测试方法的不同都有可能左右实验的结论,会影响低氧训练对骨骼肌作用的机制探讨.     

脂联素及其与运动的关系

目的:总结并分析脂联素研究进展,以及脂联素与运动的关系,为肥胖、代谢综合征、2型糖尿病、心血管疾病的治疗提供理论依据。资料来源:检索Medline1995-01/2006-10关于肥胖及运动减肥的文章。检索词"training,exercise,adiponectin,leptin"并限定文章的语种类为English。同时检索中国期刊全文数据库1994-01/2006-10关于肥胖及运动减肥的文章,限定文章语言种类为中文,检索词"运动,脂联素,瘦素"。资料选择:对资料进行初审,纳入标准:①关于脂联素的生理功能、信号转导及其与疾病的关系。②运动对脂联素的影响。排除标准:排除重复性研究。资料提炼:共收集到符合上述要求的文献213篇,对内容重复及与主题关系较远的文章进行筛除,32篇符合纳入标准。资料综合:脂联素和人的新陈代谢密切相关。主要影响脂联素的水平的因素有:脂联素复合体生物活性类型;年龄、性别、种族差异;瘦素、肿瘤坏死因子α、糖皮质激素、cAMP和β肾上腺素受体的激动剂、一氧化氮等因子的变化;其受体的活性。运动对脂联素影响方面的研究,结果有很大的不同,有人认为运动训练虽然能够改善糖尿病患者或代谢综合征的胰岛素抵抗,但并不能提高脂联素的水平;还有的研究者认为,运动训练改善胰岛素敏感性和运动训练改善了血浆中脂联素的浓度有关。结论:脂联素作为脂肪组织分泌的一种新的脂肪细胞因子,对于治疗肥胖、代谢综合征、2型糖尿病、心血管疾病具有重要的意义。目前国外对脂联素的生物功能,信号转导等进行了多方面的实验研究,而我国这方面的研究还较少。运动对脂联素的影响争议较多,需要严密对照设计的研究,以提示脂联素与运动的关系。     

卫星细胞与肌肉肥大关系及成肌因子的运动性调控

背景:卫星细胞是成体肌肉发生重要的"原料",它的增殖、分化和融合增加了肌纤维的细胞核数量或肌纤维数的数量,继而引起肌肉功能和形态学的变化,但是肌肉肥大是否一定有卫星细胞参与还存在争议.成肌因子是肌肉发生调节的核心因子,在肌肉发生的多个阶段发挥重要作用,但是目前对它们功能上特点和差异的了解仍然不够深入.目的:总结并讨论卫星细胞和成肌因子在肌肉发生和肌肉肥大以及在肌肉训练中的作用.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(2000/2010)数据库,检索词分别为"骨骼肌,肥大,运动,肌肉发生,卫星细胞,成肌因子"和"skeletal muscle,hypertrophy,exercise,myogenesis,satellite cell,MRF",语言分别设定为中文和英文.从卫星细胞与肌肉肥大、成肌因子的作用及成肌因子的运动性调控特点2方面进行总结,对卫星细胞及成肌因子在肌肉发生中的作用及其调节机制和肌肉重塑等方面进行介绍.结果与结论:共检索到177篇文章,按纳入和排除标准对文献进行筛选,共纳入30篇文章.结果表明肌肉发生是肌肉肥大的生物学基础,卫星细胞是成体肌肉发生关键,但肌肉肥大早期过程可能没有卫星细胞的参与,以DNA含量来衡量卫星细胞改变可能有较大误差,成肌因子是肌肉发生核心因子.目前研究对成肌因子成员之间功能的异同和成肌因子的运动性调控特点的了解仍不深入.     

骨形成蛋白信号转导及调控

背景:骨形成蛋白属于转化生长因子β超家族成员,具有很强的诱导成骨能力。目的:对骨形成蛋白功能、信号转导及调控机制及其信号通路异常与人类疾病的关系进行综述。方法:由第一作者用计算机检索中国期刊全文数据库(CNKI:2010)Medline(1999/2010)数据库,检索词分别为"骨形成蛋白、骨形成蛋白受体、Smad蛋白、信号转导、信号调控"和"Bone morphogenetic proteins,Bone morphogenetic proteins receptors,Smads,Signal transduction,Signaling regulation"。从骨形成蛋白的结构与功能,骨形成蛋白信号传导通路及调控,骨形成蛋白信号通路异常与人类疾病3方面进行总结。共检索到110篇文章,按纳入和排除标准对文献进行筛选,共纳入47篇文章。结果与结论:骨形成蛋白主要通过Smad依赖性和Smad非依赖性2条信号转导途径发挥作用,此过程受到细胞内外许多蛋白的调控,此外骨形成蛋白信号通路异常与人类某些疾病密切相关。     

骨骼肌重塑中的钙调神经磷酸酶信号转导通路

背景:骨骼肌重塑是骨骼肌对多种刺激因素所产生的形态结构与代谢机能的适应性变化.近几年关于钙调神经磷酸酶(CaN )/(NFATS)在骨骼肌重塑中的作用备受关注.目的:探讨钙调神经磷酸酶在骨骼肌从无氧转向有氧的代谢重塑、肌纤维类型转化以及在骨骼肌肥大过程中的信号转导作用.方法:由第一作者用计算机检索ISI Web of knowledge 数据库(1998/2010),检索词为"calcineurin,skeletal muscle,hypertrophy,NFAT,myofiber type",语言设定为英文.从钙调神经磷酸酶信号系统在骨骼肌代谢、肌纤维类型转换和肌肉肥大中的作用方面进行总结,对其调节机制、肌肉重塑等方面进行介绍.结果与结论:共检索到186 篇文章,按纳入和排除标准对文献进行筛选,共纳入33 篇文章.结果表明CaN/NFATS 信号激活有助于Ⅰ型肌纤维分化,提高线粒体有氧代谢能力,但骨骼肌对耐力运动的适应并不绝对依赖CaN.CaN/NFATS 转导通路有可能通过转录激活utrophin A 来调控骨骼肌的肥大反应.由此可知钙调神经磷酸酶参与骨骼肌代谢、纤维转化和肥大的重塑过程,调节骨骼肌对刺激产生适应性应答反应.     

Site of action of the general anesthetic propofol in muscarinic M1 receptor-mediated signal transduction

Although a potential target site of general anesthetics is primarily the GABA A receptor, a chloride ion channel, a previous study suggested that the intravenous general anesthetic propofol attenuates the M1 muscarinic acetylcholine receptor (M1 receptor)-mediated signal transduction. In the present study, we examined the target site of propofol in M1 receptor-mediated signal transduction. Two-electrode voltage-clamp method was used in Xenopus oocytes expressing both M1 receptors and associated G protein alpha subunits (Gqalpha). Propofol inhibited M1 receptor-mediated signal transduction in a dose-dependent manner (IC50 = 50 nM). Injection of guanosine 5'-3-O-(thio)triphosphate (GTPgammaS) into oocytes overexpressing Gqalpha was used to investigate direct effects of propofol on G protein coupled with the M1 receptor. Propofol did not affect activation of Gqalpha-mediated signal transduction with the intracellular injection of GTPgammaS. We also studied effects of propofol on l-[N-methyl-3H]scopolamine methyl chloride ([3H]NMS) binding and M1 receptor-mediated signal transduction in mammalian cells expressing M1 receptor. Propofol inhibited the M1 receptor-mediated signal transduction but did not inhibit binding of [3H]NMS. Effects of propofol on Gs- and Gi/o-coupled signal transduction were investigated, using oocytes expressing the beta2 adrenoceptor (beta2 receptor)/cystic fibrosis transmembrane conductance regulator or oocytes expressing the M2 muscarinic acetylcholine receptor (M2 receptor)/Kir3.1 (a member of G protein-gated inwardly rectifying K(+) channels). Neither beta2 receptor-mediated nor M2 receptor-mediated signal transduction was inhibited by a relatively high concentration of propofol (50 microM). These results indicate that propofol inhibits M1 receptor-mediated signal transduction by selectively disrupting interaction between the receptor and associated G protein.     

G蛋白偶联受体40与胰岛素分泌的关系研究现状

G蛋白偶联受体40是中、长链游离脂肪酸的特异性受体,在脂肪酸对葡萄糖刺激胰岛素分泌的调节中具有重要作用。但GPR40是否参与了脂肪酸对胰岛β细胞的脂毒性作用,以及GPR40在胰岛β细胞内信号传导途径仍不是很清楚。GPR40激动剂可能成为治疗代谢性疾病的新靶点。     

钙敏感受体及其相关信号转导通路对细胞因子分泌的调控

本文对钙敏感受体(CaSR)的结构特点、信号转导、生理作用进行了概述。重点阐述了CaSR介导的相关信号转导通路对细胞因子分泌的调控机制,并对二者关系的研究前景进行了展望。     

人粒-巨噬细胞集落刺激因子受体在NIH3T3细胞中的功能表达

目的　探讨人类粒巨噬细胞集落刺激因子（ＧＭＣＳＦ） 受体（ＧＭＲ） 在ＮＩＨ３Ｔ３ 细胞中表达的功能特性。方法　将编码人ＧＭＲα和β亚单位的ｃＤＮＡ 转染到无人ＧＭＲ表达的小鼠ＮＩＨ３Ｔ３ 细胞中,并检测其阳性转染子在配体刺激后的增殖信号传导与酪氨酸磷酸化。结果　重建的功能性ＧＭＲα／β可以介导细胞增殖与细胞集落形成,并诱导βｃ、Ｊａｋ２、Ｓｈｃ 及Ｓｈｃ 相关蛋白Ｐ１４５（ＳＨＩＰ） 酪氨酸磷酸化,然而,人ＧＭＣＳＦ并不能激活仅含ＧＭＲα的ＮＩＨ３Ｔ３ 细胞出现有丝分裂信号表达。结论　人ＧＭＲα与β亚单位同时转染入ＮＩＨ３Ｔ３ 细胞后,可通过βｃ 磷酸化,激活Ｊａｋ２ 、Ｓｈｃ 和ＳＨＩＰ信号传导途径,而导致配体依赖性细胞生长与集落形成     

Premature expression of the macrophage colony-stimulating factor receptor on a multipotential stem cell line does not alter differentiation lineages controlled by stromal cells used for coculture

We are interested to know whether expression of a lineage-specific growth factor receptor is deterministic to lineage commitment during hematopoiesis. For this purpose, we introduced the human c-fms gene into the multipotential stem cell clone LyD9 and two myeloid progenitor clones, L-GM3 and L-G3, cells that differentiate in response to granulocyte/macrophage colony-stimulating factor (GM-CSF) and granulocyte (G)-CSF, respectively. Although LyD9 cells have differentiation potential to become macrophages, c-fms transfectants of LyD9 and L-GM3 cells did not differentiate in response to human macrophage (M)-CSF. However, c-fms transfectants of L-G3 cells differentiated to neutrophils in response to human M-CSF. These results indicate that the M-CSF receptor requires a specific signal transduction pathway to exert its differentiational and proliferative effects. Furthermore, the M-CSF receptor can convey a granulocyte-type differentiation signal possibly by cooperating with the G-CSF receptor signal transduction pathway. The c-fms-transfected LyD9 cells as well as the original LyD9 cells differentiated predominantly into GM-CSF- and G-CSF-responsive cells by coculturing with PA6 and ST2 stromal cells, respectively. The results indicate that differentiation lineage is not affected by premature expression of the M-CSF receptor. Instead, the stromal cell used for coculture apparently controls lineage-selective differentiation of the multi-potential stem cell line.     

The platelet-activating factor receptor activates the extracellular signal-regulated kinase mitogen-activated protein kinase and induces proliferation of epidermal cells through an epidermal growth factor-receptor-dependent pathway

Platelet-activating factor (PAF) is a lipid mediator that has been implicated in a variety of keratinocyte functions. Keratinocytes express the specific receptor for PAF (PAF-R), a seven-transmembrane G-protein-coupled receptor. Although PAF-R-dependent stimulation of numerous signal transduction pathways has been shown in a variety of cell types, to date there has been no analysis of PAF-R signal transduction in human epidermal cells. There is also contradictory evidence that PAF acts as either a suppressor or activator of keratinocyte proliferation. Using a model system created by retroviral-mediated transduction of the PAF-R into the PAF-R-negative epidermal cell line KB, we now demonstrate that the activation of the epidermal PAF-R results in the activation of both the extracellular signal-regulated kinase (ERK) and p38, but not the jun N-terminal kinase mitogen-activated protein (MAP) kinase pathways. Additionally, we show that the activation of the PAF-R stimulates the replication of epidermal cells. The activation of the ERK signal transduction pathway, as well as the PAF-dependent increase in cell proliferation, was dependent on the transactivation of the epidermal growth factor receptor (EGF-R). PAF-R-induced transactivation of the EGF-R was blocked by pharmacologic inhibitors of matrix metalloproteinases, of heparin-binding epidermal growth factor (HB-EGF), and specific inhibitors of the EGF-R tyrosine kinase. Activation of p38 MAP kinase by the PAF-R was not dependent on EGF-R activation and represents a distinct pathway of PAF-R-mediated signal transduction. In summary, these studies provide a mechanism whereby the PAF-R can exert proliferative effects through the activation of the EGF-R.     

Agonist, antagonist, and inverse agonist characteristics of TIPP (H-Tyr-Tic-Phe-Phe-OH), a selective delta-opioid receptor ligand

Recent evidence indicates that the well established delta-opioid antagonist TIPP (H-Tyr-Tic-Phe-Phe-OH) also displays agonist activity in several cellular models. Therefore, it is possible that TIPP, and structurally related compounds, might represent a novel class of opioid agonists exhibiting unique characteristics. The purpose of this study was to examine the properties of TIPP at selected points of the signal transduction pathway (i.e., receptor binding, G-protein activation, and effector regulation) in GH(3)DORT cells (GH(3) cells expressing delta-opioid receptors) and compare them with that of an established delta-opioid agonist, [D-Pen(2),D-Pen(5)]-enkephalin (DPDPE). DPDPE exhibited properties of an agonist in all assays. In contrast, TIPP demonstrated characteristics of an agonist, antagonist, or inverse agonist, depending on the step in the signal transduction cascade examined and the assay conditions employed. In receptor binding assays, the addition of guanine nucleotides and sodium ions increased the affinity of TIPP for delta-opioid receptors in both membrane preparations and digitonin-permeabilized cells, which is characteristic of an inverse agonist. In assays measuring G-protein activation, TIPP failed to stimulate guanosine 5'-O-(3-[(35)S]thio)triphosphate ([(35)S]GTPgammaS) binding in membrane preparations, which is consistent with an antagonist profile. However, when using cells semi-permeabilized with digitonin, TIPP exhibited properties of an agonist, producing concentration-dependent, antagonist-reversible stimulation of [(35)S]GTPgammaS binding. Finally, in assays examining regulation of the intracellular effector adenylyl cyclase, TIPP exhibited characteristics of an agonist, producing inhibition of enzyme activity in both membrane preparations and whole cells. Therefore, although DPDPE and TIPP act similarly as agonists to regulate the intracellular effector adenylyl cyclase, they demonstrate significant differences in the signal transduction cascade preceding this final point of convergence.