内质网应激与炎症

内质网(endoplasmic reticulum,ER)应激是真核细胞的一种保护性应激反应,通过激活未折叠蛋白反应(unfoldedprotein response,UPR)来减少细胞内蛋白的异常聚集,从而起到细胞保护作用,而长期、严重的ER应激则会诱导细胞凋亡或死亡。能引起ER应激的因素很多,如基因突变或机体的状态改变包括氧化应激、缺血、营养不足、病毒感染和钙平衡失调等。近来研究发现,ER应激在机体的炎症反应中发挥重要作用,UPR与炎症反应通路之间通过多种机制相互偶联,参与多种炎症性疾病的发生发展。该文就近年来关于ER应激与炎症相关性的研究进展做一综述。     

活性氧与内质网应激

内质网(endoplasmic reticulum,ER)是细胞加工蛋白质和贮存Ca2+的主要场所,对应激极为敏感,其功能紊乱时出现错误折叠与未折叠蛋白在腔内聚集以及Ca2+平衡紊乱的状态,称为内质网应激(endoplasmic reticulum stress,ERS)。活性氧(reactive oxygen species,ROS)作为第二信使,在细胞生物学功能的调节中起着重要作用。细胞内氧化还原状态的改变促进了ROS的产生和凋亡诱导因子的激活,致使细胞凋亡的同时又加剧了细胞内氧化还原状态的改变。研究发现细胞内氧化还原水平的改变在ERS介导的细胞凋亡过程中承担重要的角色,推测ROS可能是ERS介导的凋亡通路的上游信号分子,该文就ROS与ERS之间的关系作一综述。     

细胞凋亡与内质网应激机制

内质网应激介导的细胞凋亡是一种新的凋亡途径,不同于死亡受体信号途径和线粒体途径.短期的内质网应激有保护细胞的作用,但是长期的内质网应激将激活一些凋亡信号分子如CHOP、JNK、Caspase,而诱导细胞凋亡.     

内质网应激与心房颤动研究进展

心房颤动（AF）是临床常见的持续性心律失常,是卒中和心力衰竭的独立危险因素,然而其具体发病机制尚不完全清楚。内质网是调控蛋白质合成、细胞内Ca2+浓度、氧化应激水平、诱导细胞凋亡信号通路的主要细胞器,在心律失常发生和发展中的作用日益受到重视。多种致病因素可导致内质网应激（ERS）,其主要通过未折叠蛋白反应（UPR）来恢复内质网稳态。ERS的过度激活可导致心房肌细胞Ca2+超载、氧化应激失衡和细胞凋亡,在AF的发病机制中发挥重要作用。本文对ERS和AF研究进展进行了综述。     

内质网应激与神经元退行性变

内质网(endoplasmic reticulum,ER)是蛋白质修饰、折叠和钙贮存的场所。ER内未折叠或错折叠蛋白积聚和钙平衡失调均可导致ER应激。早期的ER应激或未折叠蛋白反应,是一种自身代偿过程,对细胞起到保护作用,而长期、严重的ER应激则会诱导细胞凋亡及死亡。研究发现,ER应激在许多神经退行性疾病的病理机制中起重要作用。然而,确切的机制目前仍不清楚。该文就ER应激在神经元退行性变中的作用作一综述。     

内质网应激与心肌缺血再灌注损伤的关系

内质网（ER）是真核细胞内重要的膜性细胞器,参与多种生理功能平衡的调节。内质网正常的功能紊乱时就会引发内质网应激（ERS）。为了恢复ER的功能,未折叠蛋白反应（UPR）被激活,但当应激过强或持续存在时,UPR信号的慢性激活会引发细胞凋亡。内质网应激在心肌缺血再灌注损伤中的过程中,处于中心地位。故研究两者的关系,将为临床开发有效治疗心肌缺血再灌注损伤药物提供新思路。     

基于内质网应激途径的细胞保护策略的研究进展

内质网(endoplasmic reticulum,ER)是细胞内最大的细胞器,是蛋白质修饰、折叠和钙贮存的场所。ER内未折叠或错折叠蛋白积聚和钙平衡失调可导致ER应激。ER应激及其诱导的凋亡与许多疾病的发生发展密切相关。研究显示,模拟未折叠蛋白反应使蛋白质合成暂停或干预促凋亡的生物大分子能够对抗凋亡,实现ER应激诱发损伤的保护以及相关疾病的干预。     

内质网应激在肾脏疾病中的作用

内质网是存在于细胞质中的一种充满囊泡和管腔的连续性网膜状细胞器,是分泌型或结构型蛋白质进行合成、正确折叠组装、修饰的主要场所,负责合成大部分分泌性蛋白质,同时也是脂类合成及Ca2＋储存的重要场所。在病理情况下,如缺血缺氧、能量不足、糖代谢紊乱、氧化还原反应及Ca2＋浓度失衡时,以及蛋白质合成分泌增加或折叠、     

内质网应激与2型糖尿病发病机制的关系

蛋白质的错误折叠可触发细胞内质网应激,适度的内质网应激对细胞有保护作用,而过高或持续的内质网应激则导致细胞凋亡。内质网应激通过促进胰岛细胞凋亡及参与胰岛素抵抗介导了2型糖尿病的发生、发展。     

内质网应激和自噬在骨骼肌再生中的作用研究进展

骨骼肌卫星细胞(muscle satellite/stem cells, MuSCs)介导的再生和修复对骨骼肌损伤后完整肌肉功能的恢复至关重要。在多种病理生理过程中,内质网应激(endoplasmic reticulum stress, ERS)诱导的未折叠蛋白质反应(unfolded protein response, UPR)和自噬能够清除积累的错误折叠的蛋白质,是细胞维持稳态的重要机制。近年来,越来越多的研究发现在骨骼肌再生过程中内质网应激和自噬被激活,且在肌再生过程中发挥重要的调控作用,对损伤后肌肉的修复至关重要。本文主要针对近年来内质网应激和自噬在肌再生过程中的作用的研究进展做一综述,旨在为研发以内质网应激和自噬为靶点改善骨骼肌再生的药物提供理论依据。     

内质网应激在三种常见精神疾病中的研究进展

精神疾病常常表现为慢性病程,具有反复发作、慢性迁延及致残的特点,是严重影响人类健康的疾病之一.近年来精神疾病的患病率逐年升高,给社会带来了严重的疾病负担.但是,目前大部分精神疾病的发病机制尚未完全阐明.不断增加的研究证据表明,内质网应激(ERS)与精神疾病的发生发展有着密切联系,这些疾病以精神分裂症、双相障碍及抑郁障碍这三种常见精神疾病为代表.同时,研究也发现一些相关药物可能通过靶向ERS而发挥作用,提示ERS可能是精神疾病的潜在作用靶点.因此,未来深入探讨ERS在精神疾病中的具体作用机制,可为精神疾病的治疗提供新的思路.     

Endoplasmic reticulum stress mediates withaferin A-induced apoptosis in human renal carcinoma cells

The accumulation of misfolded proteins in the lumen of the endoplasmic reticulum (ER) results in cellular stress that initiates a specialized response designated as the unfolded protein response. ER stress has been implicated in a variety of common diseases, such as diabetes, ischemia and neurodegenerative disorders. Withaferin A, a major chemical constituent of Withania somnifera, has been reported to inhibit tumor cell growth. We show that withaferin A induced a dose-dependent apoptotic cell death in several types of human cancer cells, as measured by FACS analysis and PARP cleavage. Treatment of Caki cells with withaferin A induced a number of signature ER stress markers, including phosphorylation of eukaryotic initiation factor-2α (eIF-2 α), ER stress-specific XBP1 splicing, and up-regulation of glucose-regulated protein (GRP)-78. In addition, withaferin A caused up-regulation of CAAT/enhancer-binding protein-homologous protein (CHOP), suggesting the induction of ER stress. Pretreatment with N-acetyl cysteine (NAC) significantly inhibited withaferin A-mediated ER stress proteins and cell death, suggesting that reactive oxygen species (ROS) mediate withaferin A-induced ER stress. Furthermore, CHOP siRNA or inhibition of caspase-4 activity attenuated withaferin A-induced apoptosis. Taken together, the present study provides strong evidence supporting an important role of the ER stress response in mediating withaferin A-induced apoptosis.     

Andrographolide-induced apoptosis in human renal tubular epithelial cells: Roles of endoplasmic reticulum stress and inflammatory response

Andrographolide sodium bisulfate as a kind of soluble derivative of andrographolide (AD), is obviously known to be nephrotoxicity, but AD has not been reported clearly. Our study aimed to investigate the induction of apoptosis in human renal tubular epithelial (HK-2) cells by AD and its possible mechanism. Our results demonstrated that AD (0–250 μmol/L) inhibited Hk-2 cells proliferation in a dose- and time-dependent manner and induced apoptosis, accompanied by decreased of superoxide dismutase (SOD) activity and increased of malondialdehvde (MDA) content. Simultaneously, AD regulated the expression of endoplasmic reticulum (ER) molecular chaperone glucose-regulated protein 78 (GRP78/Bip) protein, elevated the expressions of C/EBP homologous protein (CHOP) and Caspase-4, indicating activation of ER stress signaling, and induced the alterative expression of kidney injury molecule-1 (KIM-1), tumor necrosis factor-α (TNF-α) and Interleukin-6 (IL-6) proteins. It provided evidence that ER stress and inflammation would be significant mechanisms responsible for AD-induced apoptosis in addition to oxidative stress.     

缺血性脑中风中与内质网应激相关炎症反应研究进展

内质网是机体微环境的重要组成结构和功能单位,内质网内稳态失衡导致的内质网应激成为近年来的一个研究热点。该文主要针对内质网应激在缺血性脑中风中的作用及相关信号通路的研究进展进行综述,特别对内质网应激触发脑中风炎症反应的机制进行了系统的整理和总结,以期为缺血性中风的防治提供新的研究思路。     

Minocycline prevents paraquat-induced cell death through attenuating endoplasmic reticulum stress and mitochondrial dysfunction

Paraquat (PQ) was demonstrated to induce dopaminergic neuron death and is used as a Parkinson's disease (PD) mimetic; however, its mechanism remains contradictory. Alternatively, minocycline is a second-generation tetracycline and is undergoing clinical trials for treating PD with an unresolved mechanism. We thus investigated the molecular mechanism of minocycline in preventing PQ-induced cytotoxicity. In this study, minocycline was effective in preventing PQ-induced apoptotic cell death, which involves the cleavages of poly (ADP-ribose) polymerase (PARP) and caspase 3 and increased fluorescence intensity of annexin V-FITC. In addition, PQ also quickly induced alterations of unfolded protein responses (UPRs) and subsequently dysfunction of the mitochondria (such as the decrease in membrane potential and increase in membrane permeability and superoxide formation). Finally, the mechanism of minocycline in preventing PQ-induced apoptosis might be mediated by attenuating endoplasmic reticulum (ER) stress and mitochondrial dysfunction, which respectively results in caspase-12 activation and the release of H₂O₂, HtrA2/Omi, and Smac/Diablo. Thus, minocycline could possibly be used to treat other neurodegenerative disorders with similar pathologic mechanisms.     

积雪草酸对高糖培养肾小球系膜细胞内质网应激的影响

目的 探讨积雪草酸(AA)对高糖培养肾小球系膜细胞(HBZY-1)内质网应激的影响.方法 HBZY-1细胞随机分为五组:高糖对照组(A组)、高糖加不同浓度AA组(B组30 μmol/L、C组60μmol/L、D组90 μmol/L)和空白对照组(E组).分别培养12和24 h后,Western blot法检测蛋白激酶样内质网激酶(PERK)、磷酸化PERK (P-PERK)、C/EBP同源蛋白(CHOP)和天冬氨酸特异性半胱氨酸蛋白酶12(Caspase-12)的表达.结果 与E组相比,A组培养12和24 h后的PERK表达降低,P-PERK、CHOP和Caspase12表达增加(P＜0.05).与A组相比,培养12h后C、D组和培养24 h后B、C、D组的PERK表达均增加,P-PERK、CHOP和Caspase-12表达降低(P＜0.05).上述变化均可见浓度依赖性.结论 AA可能通过下调CHOP和Caspase-12蛋白的表达对糖尿病大鼠肾脏起到保护作用.