脑缺血/再灌注损伤后内质网应激对神经元转归的影响

内质网本身在细胞生理及组成结构方面起至关重要的作用,当内质网出现功能障碍时,未折叠蛋白反应(UPR)试图增加未折叠蛋白的折叠能力而减轻内质网应激(ERS)的压力。当无法缓解时,细胞便通过内质网凋亡途径走向凋亡。而脑缺血/再灌注损伤(CIRI)会导致内环境紊乱,引起ERS反应,进而通过ERS途径引起神经元凋亡。现对内质网的结构、功能、ERS机制、ERS后产生的UPR机制以及凋亡机制予以阐述,并提出了对CIRI后ERS状态下神经元转归的应对措施。     

内质网应激与免疫炎症反应的研究进展

内质网是具有重要生理功能的细胞器,是细胞内Ca2+贮存器,负责蛋白的生物合成、折叠、组装和修饰。内质网对各种刺激非常敏感,蛋白折叠需求增强或外界刺激等因素,均可引起内质网蛋白折叠负荷与蛋白折叠能力之间的不平衡,造成未折叠蛋白或错误折叠蛋白在内质网腔内蓄积,即诱发内质网应激(endoplasmic reticulum stress,ERS)。为了确保蛋白折叠的精准性,防止未折叠蛋白或错误折叠蛋白在内质网腔内蓄积,     

内质网应激与肿瘤关系的研究进展

内质网是真核细胞蛋白质修饰、折叠、组装、分泌的重要场所,同时也是细胞内钙离子储存的场所。当机体受到氧化应激、缺血缺氧、营养不良、病毒感染和钙平衡失调等病理生理因素影响时,未折叠蛋白或错误折叠蛋白在内质网腔内积聚导致细胞内钙稳态失衡,打破内质网稳态,最终引起内质网应激（endoplasmic reticulum stress,ERS）。近年来随着对ERS研究的不断深入,发现ERS在肿瘤的发生、发展、转移、预后及凋亡中均发挥着非常重要的作用［1］。本文对ERS与肿瘤关系进行综述,为探索肿瘤的形成机制及临床防治提供新的理论依据。     

未折叠蛋白反应与胰腺β细胞功能的研究进展

胰腺β细胞功能障碍导致糖尿病发生,在糖尿病早期,胰腺β细胞通过自身调节代偿高血糖和外周胰岛素抵抗,涉及的信号通路之一称为未折叠蛋白反应(UPR)。UPR不但可以维持内质网(ER)动态平衡和β细胞完整性,而且在ER折叠中起重要作用,UPR可以加快错误折叠蛋白降解,还可以抑制信使RNA(mRNA)转录,从而减少内质网腔内未折叠蛋白的堆积。该文着重阐述UPR在糖尿病期间的β细胞代偿和衰竭中的主要作用。     

内质网应激与细胞凋亡

内质网(ER)是细胞内重要的细胞器,参与多种细胞进程,这些进程对于维持细胞存活和发挥细胞的正常生理功能具有重要的作用。然而在多种生理病理条件下,内质网稳态会发生变化而失衡,从而诱发内质网应激(ERS),此时机体通过激活未折叠蛋白反应(UPR)来恢复内质网的正常功能。当持续的ERS状态无法恢复时,ERS就会触发细胞凋亡程序,通过不同的凋亡途径引起细胞凋亡。     

内质网应激和糖脂代谢紊乱的关系及中药干预研究

内质网是细胞内重要的钙离子贮存器,也是蛋白合成后修饰、折叠及转运的重要场所.在细胞缺乏能量、脂质过度负荷、钙离子稳态失衡、分泌蛋白合成增加等条件下,新生肽链的修饰、折叠、组装受到干扰,将引起未折叠蛋白在内质网中堆积,使细胞发生内质网应激 (endoplasmic reticulum stress,ERS).     

内质网应激及其与肿瘤能量代谢关系的研究进展

内质网具有多种功能,当其稳态发生失衡时,便会发生内质网应激(endoplasmic reticulum stress,ERS).内质网会启动名为未折叠蛋白应答(unfolded protein response,UPR)的高度调节机制,保护细胞免受错误折叠蛋白的积累.肿瘤代谢与ERS有着密不可分的联系,多种人类肿瘤中都...     

内质网应激与膜性肾病

内质网(endoplasmic reticulum,ER)是调节蛋白质合成、折叠及组装的重要场所。各种原因如ER中Ca2+缺乏均可引起ER功能紊乱,使蛋白质从ER向高尔基体的转运受阻[1],最终引发内质网应激(endoplasmic reticulum stress,ERS)。细胞通过激活未折叠蛋白反应(the unfolded protein response,UPR)保护ERS引起损伤的细胞,强烈或持久的ERS又可启动UPR的促凋亡信号。肾病尤其是膜性肾病(membranous nephropathy,MN)的发生发展与ERS密切相关,文中主要阐述ERS在MN发病机制中的作用。     

内质网应激与吸入麻醉药引起的认知功能障碍的研究进展

内质网(ER)广泛存在于真核细胞中,其内环境的稳定是实现ER功能的基本条件,ER内未折叠或错折叠蛋白积聚和钙平衡失调均可导致内质网应激(ERS),而长期、严重的ERS则会诱导细胞凋亡及死亡。ERS在神经退行性疾病病理机制中的作用已成为近年来的热点,国内外关于ERS与临床疾病的相关     

内质网应激与蛋白质错误折叠相关疾病的研究进展

蛋白质的错误折叠会导致疾病。错误折叠蛋白质在内质网中滞留和蓄积会触发内质网应激（ERS）和未折叠蛋白反应。既往研究已经证实ERS与蛋白质错误折叠相关疾病有密切联系。本文将阐述ERS以及其在蛋白质错误折叠相关疾病中的研究进展,为临床治疗这类疾病提供新的理论依据。     

内质网应激在眼科疾病中的研究进展

内质网是一种负责蛋白质合成、折叠以及转运,脂类生物合成,空泡运输以及胞内钙存储的多功能细胞器。内质网腔内未折叠蛋白质的蓄积及钙离子稳态的打破,诱发内质网应激,发生具有保护性的未折叠蛋白反应。内质网应激与多个信号通路相互联系,参与炎症、凋亡的发生发展,近年来得到越来越多的关注。本文就内质网应激发生机制及相关的眼科疾病的研究进展作一综述。     

内质网应激与血管内皮细胞凋亡的研究进展

内质网应激(ERS)凋亡途径是继死亡受体信号途径和线粒体途径后发现的一种新的细胞凋亡途径。虽然该途径早期通过激活未折叠蛋白反应使细胞内蛋白质合成暂停、内质网稳态恢复,起到细胞保护作用,但当机体诱导ERS的因素持续存在,ERS也将持续进行,并会触发C/EBP同源蛋白、c-JUN氨基末端激酶及caspase等通路诱导细胞凋亡。血管内皮细胞损伤及凋亡是各种疾病和病理生理过程的重要环节,大量研究表明,血管内皮细胞凋亡与ERS密切相关,通过干预ERS可以有效对抗其凋亡,起到保护血管内皮的作用。本文总结了ERS及其参与血管内皮细胞凋亡机制的研究进展。     

Endoplasmic Reticulum Stress Induced by Tunicamycin and Antagonistic Effect of Tiantai No.1(天泰1号) on Mesenchymal Stem Cells

<正>Objective:Changes of the internal and external cellular environments can induce calcium homeostasis disorder and unfolded protein aggregation in the endoplasmic reticulum(ER).This ER function disorder is called endoplasmic reticulum stress(ERS).Severe long-term ERS can trigger the ER apoptosis signaling pathway,resulting in cell apoptosis and organism injury.Recent researches revealed that ERS-induced cell death was involved in the neurocyte retrogradation in the progress of neuron degenerative diseases,such as Alzheimer's disease(AD),Parkinson's disease and so on.Therefore,the protection effect of the traditional Chinese drug——Tiantai No.1(天泰1号) on the ERS injury of AD was investigated at the molecular gene level in this study with a view to explore the gene pharmacodynamic actions and mechanisms of this drug.Methods: Primarily cultured marrow mesenchymal stem cells(MSCs) of rats were treated by tunicamycin(TM) in order to induce ERS.RT-PCR,fluorescence immunocytochemistry and Western blot techniques were used to determine the mRNA and protein expression levels of the protective stress protein-ER molecular chaperones GRP78 and GRP94(which would assist cells to resist cellular stress injury),and to determine the mRNA and protein expression levels of apoptosis promoting molecule Caspase-12 on the membrane of the ER,respectively. Results:Protein expression levels of GRP78 and GRP94 were significantly increased in the TM-induced MSCs, and the mRNA level of Caspase-12 was also remarkably increased in the TM-induced MSCs(P0.05).All these proved that the ERS model was successfully established by TM in MSC.Meanwhile,the mRNA and protein levels of GRP78 and GRP94 were all significantly increased compared with the model group(P0.05 or P0.01) after MSCs were treated with Tiantai No.1 while the mRNA and protein expression levels of Caspase-12 were significantly decreased compared with the model group(P0.05 or P0.01).This effect showed a dose dependent manner.Conclusion:Tiantai No.1 might attenuate the cell apoptosis induced by ERS injury,and thus protect the neurons against AD.     

内质网应激与支气管哮喘

内质网应激是细胞对于内源性应激的一种适应性反应,由未折叠蛋白所诱导,其机制被称为未折叠蛋白反应(UPR)。哺乳动物UPR包含3个经典的分支通路,分别以胰腺内质网激酶(PERK)、需肌醇跨膜激酶/核酸内切酶1(IRE1)和活化转录因子6(ATF6)作为近端效应物,能够促进蛋白质折叠和转运,停止蛋白质的翻译合成,降解清除错误蛋白,并可启动凋亡程序诱导不能修复错误蛋白的细胞凋亡,从而维持内环境与组织细胞功能的稳态。支气管上皮内含多种蛋白质合成分泌旺盛的细胞类型,本身易出现内质网应激;支气管哮喘时,气道炎症状态等因素的存在被认为可以诱发UPR,并与气道炎症反应互为因果,交互作用。目前的研究认为,在支气管哮喘发病中,气道上皮细胞的钙稳态失调、透明质酸与黏蛋白的异常分泌、细胞因子对炎细胞的募集作用以及免疫调节状态的异常等环节与内质网应激存在密切的关系。本文即对内质网应激与哮喘的相关研究作一综述。     

Endoplasmic reticulum stress-induced apoptosis in the development of reproduction

Proteins synthesized in the endoplasmic reticulum(ER) are properly folded with the assistance of ER chaperones. Accumulation of misfolded protein in the ER triggers an adaptive ER stress(ERS) response termed the unfolded protein response. Recent interest has focused on the possibility that the accumulation of misfolded proteins can also contribute to reproductive response, including preimplantation embryos, testicular germ cell, placenta, and unexplained intrauterine growth restriction(IUGR). The major ERS pathway constituents are present at all stages of preimplantation development and that the activation of ERS pathways can be induced at the 8-cell, morula and blastocyst stage. This review mainly introduced the research progress of ERS induced apoptosis of reproductive cells, providing a new direction for the research of reproductive disease therapy.     

癫痫脑损伤与内质网应激的研究进展

近年来的研究表明,单次癫痫发作即可产生脑损伤。其主要的病理改变是神经元程序性死亡和神经胶质增生;其原因是细胞内外环境的改变,诱导内质网应激启动自适应性保护通路即未折叠蛋白反应。当长时间且强烈的内质网稳态失衡时,可启动内质网应激反应性凋亡通路,这一系列细胞内信号转导和相关基因的激活被视为一条新的细胞信号路径,为癫痫脑损伤防治的研究提供了新方向。     

内质网应激中ATF-6调控细胞凋亡及相关疾病

许多异常反应都会引起内质网应激,进而激活未折叠蛋白反应。当未折叠反应仍不能缓解内质网蛋白负荷时,就会通过多条途径引起细胞凋亡,并引起相关疾病,如糖尿病,躁郁症,神经退行性疾病和创伤后应激反应PTSD等。该文主要论述活化转录因子6在ER应激中调控细胞凋亡的机制以及引起的相关疾病。     

Role of Endoplasmic Reticulum Stress in Silica-induced Apoptosis in RAW264.7 Cells

Objective We investigated the role of endoplasmic reticulum stress(ERS) in silica-induced apoptosis in alveolar macrophages in vitro. Methods RAW264.7 cells were incubated with 200 μg/mL silica for different time periods. Cell viability was assayed by the MTT assay. Cell apoptosis was evaluated by DAPI staining, flow cytometry analysis, and Western blot analysis of caspase-3. Morphological changes in the endoplasmic reticulum were observed by transmission electron microscopy. The expression of ERS markers binding protein(BiP) and CCAAT-enhancer-binding protein homologous protein(CHOP) was examined by Western blotting and real-time PCR. As an inhibitor of ERS, 4-phenylbutyric acid(4-PBA) was used in the experiments. Results Silica exposure induced nuclear condensation and caspase-3 expression in RAW264.7 cells. The number of apoptotic cells increased after silica exposure in a time-dependent manner. Silica treatment induced expansion of the endoplasmic reticulum. In addition, the expression of BiP and CHOP increased in silica-stimulated cells. Furthermore, 4-PBA treatment inhibited silica-induced endoplasmic reticulum expansion and the expression of Bi P and CHOP. Moreover, 4-PBA treatment attenuated nuclear condensation, reduced apoptotic cells, and downregulated caspase-3 expression in silica-stimulated cells. Conclusion Silica-induced ERS is involved in the apoptosis of alveolar macrophages.