内质网应激在急性肺损伤中的研究进展

内质网是细胞内重要的细胞器之一,主要参与蛋白质的加工和修饰,引导其正确的折叠与组装.在各种刺激因素如感染、氧化应激等的作用下,内质网会发生功能紊乱,导致内质网应激(endoplasmic reticulum stresses,ERS).持续的ERS可导致未折叠蛋白反应(unfolded protein response...     

内质网应激在糖尿病及糖尿病肾病中的研究进展

内质网（ER）是细胞内重要的细胞器,多种因素可导致ER内稳态失衡,功能发生改变,称为内质网应激（ERS）。ERS首先触发未折叠蛋白反应,增强细胞的存活能力。如果ERS持续存在,各种刺激超出了细胞处理能力,则将启动相关凋亡途径诱导细胞凋亡。越来越多的研究表明,ERS在糖尿病及其并发症脏器损害过程中普遍存在并发挥着重要作用。     

内质网应激与心血管疾病

内质网应激是细胞内一种适应性机制,持续或过强的内质网应激则诱导细胞凋亡,造成组织损伤.多项研究显示内质网应激是多种心血管疾病如动脉粥样硬化、缺血性心脏病、心肌肥大、心力衰竭及糖尿痛心肌病等发生、发展的共同通路,干预内质网应激可能成为心血管疾病治疗的新靶点.     

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。     

内质网应激与肿瘤治疗

细胞要想达到最佳状态就必须维持一个持续的稳态。内质网(endoplasmic reticulum,ER)是一个具有多功能的重要细胞器,它也是维持体内平衡的重要场所。当多种因素干扰ER功能时,就会激活一种被称为"内质网应激(endoplasmic reticulum stress,ERS)"的现象来启动多种途径来缓解相关的损害,这些途径总称为未折叠蛋白质反应(unfolded protein response,UPR)。UPR一方面它在一定程度上能够缓解ERS带来的相关损害;另一方面如果ERS持续并且过度,那么UPR也可以诱导细胞凋亡。在某些极端环境下肿瘤细胞会表现出极强的适应能力且越来越多的研究表明这种能力在一定程度上是由于UPR状态的改变所引起的。虽然在肿瘤治疗中ERS和UPR的作用仍不十分清楚,但仍有希望在未来的抗肿瘤治疗中的成为治疗新靶点。     

内质网应激在丙肝病毒感染发病学中作用的研究进展

丙型肝炎病毒(HCV)常扰乱内质网稳态,其复制中间产物的积累可导致内质网应激(ERS),与多种疾病的发生密切相关.为了应对内质网应激所带来的有害影响,细胞激活未折叠蛋白反应(UPR)和凋亡通路.在病毒感染的初期,未折叠蛋白反应主要用于清除病毒产生的蛋白和其他中间产物;而当感染进一步深化,稳态不能维持时细胞则激活凋亡通路...     

低氧微环境下内质网应激及其相关疾病

内质网应激是细胞应激的重要组成部分,是真核细胞的一种保护性反应。氧分压改变（如低氧）是重要的应激条件,显著影响细胞的生物学表型及细胞行为（生存、迁移及侵袭等）。细胞通过内质网应激降低胞内未折叠蛋白的浓度,抑制未折叠蛋白凝集的发生。近来发现内质网应激与肿瘤、糖尿病及炎症等多种疾病的发生、发展密切相关,组织局部的低氧微环境是这些疾病的特征之一。因此对低氧导致的内质网应激的发生及其机制的研究,对肿瘤、心血管疾病及糖尿病等疾病治疗新策略的发展具有重要意义。     

内质网应激介导细胞凋亡及免疫炎症反应的研究进展

内质网是一种细胞器,可以使新合成的蛋白质通过甲基化、羟基化、脂化或形成二硫键正确折叠。内质网应激(endoplasmic reticulum stress,ERS)是由内腔中未折叠蛋白的积累引起的细胞应激反应。为应对ERS,细胞建立了一种进化保守的机制,称为未折叠蛋白反应(unfolded protein respon...     

内质网应激在低氧性肺动脉高压中作用的研究进展

低氧性肺动脉高压(HPH)是长期低氧导致的血管持续性收缩和血管不可逆重塑的严重肺部并发症。低氧可干扰内质网腔内蛋白质折叠过程,激活内质网应激(ERS)。ERS作为细胞应激的核心反应,与HPH的发生发展关系密切。     

内质网应激在肺肿瘤中的作用

内质网是细胞的蛋白质加工厂,主要负责蛋白质的合成、折叠和装配。各种生理和病理条件（如缺氧、氧化还原状态的变化）可能会干扰内质网的功能,并导致未折叠蛋白在内质网中积累,导致内质网应激（endoplasmic reticulum stress,ERS）。ERS是细胞抵抗外来不良刺激的一种重要保护机制,也是决定细胞命运的关键。适度的ERS能够促进肺肿瘤细胞生存和转移,过度的ERS则促进肺肿瘤细胞凋亡。多种抗肿瘤药物都可通过加重ERS而促进肺肿瘤细胞凋亡。     

Role of endoplasmic reticulum stress and protein misfolding in disorders of the liver and pancreas

The endoplasmic reticulum (ER) is the site of synthesis and folding of membrane and secretory proteins. The fraction of protein passing through the ER represents a large proportion of the total protein in the cell. Protein folding, glycosylation, sorting and transport are essential tasks of the ER and a compromised ER folding network has been recognized to be a key component in the disease pathogenicity of common neurodegenerative, metabolic and malignant diseases. On the other hand, the ER protein folding machinery also holds significant potential for therapeutic interventions. Many causes can lead to ER stress. A disturbed calcium homeostasis, the generation of reactive oxygen species (ROS) and a persistent overload of misfolded proteins within the ER can drive the course of adisease. In this review the role of ER-stress in diseases of the liver and pancreas will be examined using pancreatitis and Wilson´s disease as examples. Potential therapeutic targets in ER-stress pathways will also be discussed.     

动脉粥样硬化中巨噬细胞凋亡与内质网应激机制

巨噬细胞是机体免疫系统的重要细胞成份,具有多种生理功能,在动脉粥样硬化等血管疾病的发生和发展中具有重要作用.巨噬细胞凋亡是造成动脉粥样硬化斑块不稳定的重要因素,在晚期动脉粥样硬化中,内质网应激与巨噬细胞凋亡密切相关.目前已知的巨噬细胞凋亡途径包括外源性的死亡受体途径、内源性的线粒体途径及内质网应激凋亡途径,其中内质网应...     

The expanding roles of endoplasmic reticulum stress in virus replication and pathogenesis

Abstract

The endoplasmic reticulum (ER) is a cellular membrane organelle that plays important roles in virus replication and maturation. Accumulating evidence indicates that virus infection often disturbs ER homeostasis and leads to ER stress, which is associated with a variety of prevalent diseases. To cope with the deleterious effects of virus-induced ER stress, cells activate critical signaling pathways including the unfolded protein response (UPR) and intrinsic mitochondrial apoptosis, which have complex effects on virus replication and pathogenesis. In this review, we present a comprehensive summary of recent research in this field, which revealed that about 36 viruses trigger ER stress and differentially activate ER stress-related signaling pathways. We also highlight the strategies evolved by viruses to modulate ER stress-related signaling networks including immune responses in order to ensure their survival and pathogenesis. Together, the knowledge gained from this field will shed light on unveiling the mechanisms of virus replication and pathogenesis and provide insight for future research as well as antiviral development.     

Enhanced apoptotic and reduced protective response in chondrocytes following endoplasmic reticulum stress in osteoarthritic cartilage

Endoplasmic reticulum (ER) stress has been shown to participate in many disease pathologies. Although recent reports have demonstrated that ER stress in chondrocytes is present in human osteoarthritis (OA), its role in the pathology of cartilage degeneration, such as chondrocyte apoptosis, remains unclear. In the present study, we investigated the expression of phosphorylated PERK (pPERK), ubiquitin (Ub), GRP78, CHOP, phosphorylated JNK (pJNK) and cleaved caspase-3 (C-CASP3) and the mRNA splicing of XBP1 (XBP1 splicing) in human OA cartilage by immunohistochemistry and RT-PCR. Additionally, human chondrocytes were treated with several concentrations of tunicamycin, an ER stress inducer, to assess the impact of ER stress on the mRNA expression of CHOP, XBP1 splicing and apoptosis, as determined by real-time PCR, RT-PCR and ELISA analyses respectively. In human OA cartilage, the number of chondrocytes expressing pPERK, Ub, CHOP and pJNK positively correlated with cartilage degeneration and the number of C-CASP3-positive chondrocytes. XBP1 splicing and GRP78 expression in severe OA containing the greatest number of C-CASP3-positive chondrocytes were similar to the levels in mild OA, however, XBP1 splicing was higher in moderate OA than in mild and severe OA. Tunicamycin dose dependently increased CHOP expression and apoptosis of cultured chondrocytes. Although tunicamycin upregulated XBP1 splicing in cultured chondrocytes, its impact on XBP1 splicing was weakened at higher concentrations. In conclusion, the present results indicate that ER stress may contribute to chondrocyte apoptosis along with OA progression, which was closely associated with an enhanced apoptotic response and a reduced protective response by the cells.     

Bevacizumab induces A549 cell apoptosis through the mechanism of endoplasmic reticulum stress in vitro

Aims: To observe the effect of bevacizumab on human A549 cells and explore its mechanism. Methods: After different concentrations (0 μM, 1 μM, 5 μM, 25 μM) of bevacizumab treating in A549 cells, CCK8 assay detect the impact of bevacizumab on A549 cell proliferation and flow cytometry determine the effect of bevacizumab on human A549 cells apoptosis. Real-time PCR and Western blotting detect the changing expression of the target gene (CHOP, caspase-4, IRE1, XBP-1) on mRNA and Protein level. Results: Treatment with bevacizumab for 24-hr have induced cell death in a does-dependent manner dramatically (P<0.05). In terms of the mRNA level, expression of XBP-1 has increased obviously in each group (1 μM, 5 μM, 25 μM) (P<0.01); the expression of CHOP (25 μM) and caspase-4 (5 μM) have increased slightly (P<0.05). In terms of the protein level, the expression of CHOP has increased obviously in each group (1 μM, 5 μM, 25 μM) when compared with the control group (0 μM) (P<0.05). As for caspase-4 (5 μM, 25 μM), the expression have increased slightly when compared with the control group (0 μM) (P<0.05). Conclusion: Bevacizumab can induce A549 cell apoptosis through the mechanism of endoplasmic reticulum stress.