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...     

内质网应激与动脉粥样硬化的研究进展

内质网(ER)是真核细胞复杂的膜结构,参与蛋白质折叠、脂质合成,调节细胞Ca2+摄取、储存和信号传导,并参与细胞脂质的产生。内质网蛋白质折叠能力可以达到饱和,从而诱导内质网应激(ERS)反应。越来越多的证据表明,在动脉粥样硬化病变的病理条件下,ERS与细胞凋亡和炎症有关,并有助于动脉粥样硬化的进展。ERS在动脉粥样硬化病变中不同类型细胞中的作用,包括长期ERS诱导的凋亡和炎症途径的激活,尤其是在晚期病变巨噬细胞和内皮细胞(ECs)中,以及不同病变细胞中常见的动脉粥样硬化相关内质网应激源,都有助于动脉粥样硬化的临床进展。鉴于ERS和未折叠蛋白反应(UPR)信号通路在动脉粥样硬化和心血管疾病中的重要作用,针对这些过程来减轻ERS可能是一种新的治疗策略。     

动脉粥样硬化中炎性反应与内质网应激的相互作用

炎性反应和内质网应激均是动脉粥样硬化发生和发展过程中的重要事件。炎性反应可通过多条途径诱发内质网应激,而内质网应激在疾病的不同阶段可抑制或者促进炎性反应。     

功能静止型嗜铬细胞瘤29例临床分析简

 目的 回顾性分析29例功能静止型嗜铬细胞瘤的临床资料,以提高其诊治水平。 方法 分析2010年5月至2013年5月在北京协和医院接受手术并经病理证实的功能静止型嗜铬细胞瘤患者29例,总结患者年龄、肿瘤部位、肿瘤最大径、手术方式、术中血压变化、尿儿茶酚胺以及术前核医学检查等方面的临床特点。结果 患者血压正常,尿儿茶酚胺正常或稍高,肿瘤位于双侧肾上腺1例,右侧肾上腺13例,左侧肾上腺15例,直径1.5~14cm。腹腔镜手术切除25例,开放手术切除4例。23例术前接受药物准备,术中血压平稳,6例术前未行药物准备,其中2例术中出现血压剧烈波动。23例术前行生长抑素受体显像的患者中,有11例未见异常;11例术前行131IMIBG显像,1例未见异常。结论 对于功能静止型嗜铬细胞瘤,尿儿茶酚胺及生长抑素受体显像敏感性较低,对于CT表现可疑的,建议术前行131IMIBG显像,一旦确诊,应该在充分药物准备的基础上接受手术治疗。     

云南省蒙古族9项头面部群体遗传学特征简

 目的 了解云南蒙古族头面部群体遗传学特征。方法 采用随机整群抽样法调查云南省通海县208例（男性105例,女性103例）蒙古族9项头面部群体遗传学指标。结果 1）云南蒙古族有内眦褶率89.5%,上眼睑皱褶率91.4%,铲型门齿率96.19%,凸鼻梁率32.4%,宽鼻孔率80%,突型下颏率32.4%,耳垂率76.2%,额头发际有尖率21%,卷发率7.7%;2）除了耳垂类型和鼻梁类型外,其余7项指标类型出现率在性别间均无显著性差异;3）9项特征彼此间相关性极小;4）与内蒙古9个蒙古族人群相比,多存在极显著差异。结论 与北方内蒙古蒙古族群体差异较大。     

内质网应激参与糖脂毒性引起的胰岛β细胞凋亡

 胰岛β细胞具有高度发达的内质网,是对内质网应激最敏感的细胞之一。高浓度的游离脂肪酸引起内质网应激反应进而诱导了β细胞的凋亡,葡萄糖则促进了脂肪酸通过内质网应激引起的β细胞凋亡。总之,内质网应激介导了糖脂毒性引起的β细胞凋亡。     

PTEN对髓系白血病细胞VEGF及MMP表达的影响简

 目的 探讨在慢性髓系白血病中与张力蛋白同源的10号染色体缺失的磷酸酶基因(PTEN)对血管内皮生长因子(VEGF)及金属基质蛋白酶(MMP)相互影响及其作用机制。方法 1)研究10例慢性髓系白血病慢性期CML-CP、10例急变期CML-BC及10例正常人骨髓单个核细胞内PTEN、VEGF、MMP-2和MMP-9 mRNA表达水平变化。2)将携带有野生型PTEN和绿色荧光蛋白的腺病毒（Ad-PTEN-GFP）及对照载体腺病毒（Ad-GFP）转染人慢性髓系白血病细胞系K562。MTT检测细胞增殖;荧光定量PCR（FQ-PCR）检测PTEN、VEGF、MMP-2和MMP-9 mRNA水平变化,Western blot及明胶酶谱检测PTEN、p-Akt、VEGF、MMP-2和MMP-9蛋白表达。结果 CML-BC患者中PTEN mRNA表达水平低于CML-CP及正常对照组(P<0.05),而VEGF、MMP-2、MMP-9 mRNA在CML-BC患者中均高于CML-CP及正常对照组(P<0.05)。以MOI=200转染K562细胞3d后Ad-PTEN-GFP组K562细胞内VEGF、MMP-2、MMP-9 mRNA表达水平均明显低于Ad-GPF组和未转染组(P<0.05),PTEN与VEGF、MMP-2、MMP-9 mRNA表达水平负相关,转染Ad-PTEN-GFP组与转染Ad-GFP组比较VEGF、MMP-2、MMP-9 mRNA表达水平分别降低4.80、5.88、5.72倍,p-Akt及VEGF、MMP-2、MMP-9蛋白表达水平分别降低26.0、5.23、2.86、4.76倍。结论 PTEN基因可能通过抑制VEGF、MMP-2、MMP-9表达,抑制髓系白血病细胞血管新生及侵袭。     

YAP蛋白与肿瘤简

 Hippo-YAP 信号通路是新发现的生长控制信号通路, 能够限制调结细胞的生长增殖, 细胞凋亡, 信号通路异常有利于肿瘤的发生。YAP蛋白还参与调控AKT-mTORC、WNT和MAPK等信号通路,进而影响肿瘤细胞的生长和侵润转移。YAP蛋白在多种类型的人类肿瘤中表达异常增加,或许成为肿瘤新的治疗靶点。     

互联网在外科临床教学中的意义简

 分析在互联网时代,互联网给外科教学带来的影响,通过分析其在外科教学过程中的应用,以便充分合理地利用互联网资源,更好地提高外科教学效果。     

Role of Herp in the endoplasmic reticulum stress response

Application of differential display to cultured rat astrocytes allowed cloning of Herp cDNA. Although Herp was strongly induced by endoplasmic reticulum (ER) stress, it decayed rapidly consequent to proteasome-mediated degradation. To investigate the role of this molecule in terms of the stress response, Herp knockout cells were developed using F9 embryonic carcinoma cells. F9 Herp null cells were more vulnerable to ER stress compared with F9 wild-type cells. In the early period of ER stress (0-8 h after tunicamycin treatment), Herp null cells displayed enhanced ER stress signalling and stabilization of an endogenous ERAD substrate, compared with wild-type cells. In the intermediate period (8-20 h after tunicamycin treatment), Herp null cells displayed reduced ER stress signalling, whereas in the late period (20-40 h after tunicamycin treatment), Herp null cells manifested irreversible cellular changes that lead to apoptotic cell death. Transfection analysis revealed that the N-terminal region, including the ubiquitin-like domain of Herp, was required for the survival of F9 cells under ER stress. These results indicate that Herp is a short-lived Ub-like protein improving the balance of folding capacity and protein loads in the ER and plays crucial roles for the ER stress resistance in F9 cells.     

内质网应激中IRE1级联反应对动脉粥样硬化的作用

正1概述内质网(endoplasmic reticulum,ER)蛋白质折叠在生理上是至关重要的,它的破坏导致内质网应激(endoplasmic reticulum stress,ERS)触发动脉粥样硬化(atherosclerosis,AS)发生发展。未折叠蛋白反应(unfolded protein response,UPR)是目前研究最为透彻的ERS信号通路,一定程度的UPR有利于维持     

Serpinopathy and endoplasmic reticulum stress

We have recently identified a novel human gene, megsin, which is a new serine protease inhibitor (serpin) predominantly expressed in the kidney. Our previous studies suggested a role of megsin in the pathogenesis of human renal diseases, but its exact biopathological significance remained unknown. During the analysis of experimental animals overexpresssing the human megsin gene, we unexpectedly generated a serpinopathy model involving the kidney and pancreas and discovered a novel mechanism of renal injury, that is, cellular damage by endoplasmic reticulum (ER) stress caused by conformational disorder of protein tertiary structure within the ER. In vitro induction of ER stress may play a role in renal cell injury by various stimuli, but the involvement of ER stress in human renal disease remains elusive. Further research for ER structure and function may open new exciting prospects in the pathology of human renal diseases.     

软骨细胞凋亡与内质网应激

背景：软骨细胞的凋亡最终会导致骨关节炎的发生。目前发现的软骨细胞凋亡机制有很多,但内质网应激引起其凋亡的机制尚处于初始阶段。目的：综述分析内质网应激如何引起软骨细胞凋亡,并探寻骨关节炎治疗的新方法。方法：第一作者通过计算机检索,检索了PubMed、CNKI、万方数据库2000年1月至2015年1月的相关文献。使用PubMed检索时,输入检索词“endoplasmic reticulum stress,chondrocyte,apoptosis”之间以“AND”形式连接,使用CNKI、万方数据库检索时,输入主题词“内质网应激,软骨细胞,凋亡”之间以“并且/与”连接,选择模糊查询进行检索。选择文章内容涉及骨关节炎的文献,较多采用近期发表在权威杂志上的相关文献。结果与结论：初检得到中英文文献共计62篇,其中57篇符合纳入标准,对其进行综述。PERK、IRE1和ATF6三条信号通路对软骨细胞同样有重要作用。内质网应激介导的细胞凋亡机制有未折叠蛋白质反应和Ca²⁺起始信号2种,但具体机制及凋亡途径间的交叉作用还未明了。若从上述信号通路中探索软骨细胞凋亡效应的抑制分子,并将其作为治疗骨关节炎的靶点,可能会为治疗骨关节炎提供新的方法。中国组织工程研究杂志出版内容重点：组织构建;骨细胞;软骨细胞;细胞培养;成纤维细胞;血管内皮细胞;骨质疏松;组织工程     

一氧化氮和内质网应激

一氧化氮(nitric oxide,NO)是一种重要的多功能内源性气体分子,能舒张血管、参与免疫反应和作为一种神经递质在神经元的信息传递中发挥重要作用,因而广泛参与机体心血管系统、神经系统和免疫系统等的生理和病理调节[1].     

Endoplasmic reticulum stress and the inflammatory response in allergic contact dermatitis

Maintaining homeostasis is central to organismal health. Deviation is detected by a variety of sensors that react to alarm signals arising from injury, infection, and other inflammatory triggers. One important element of this alarm system is the innate immune system, which recognizes pathogen-/microbe- or damage-associated molecular patterns via pattern recognition receptors localized in the cytosol or in membranes of innate immune cells such as macrophages, dendritic cells, and mast cells but also of T cells, B cells, and epithelial cells. Activation of the innate immune system results in inflammation and is a pre-requisite for activation of the adaptive immune system. Another important element is represented by the unfolded protein response (UPR), a stress response of the endoplasmic reticulum. The UPR regulates proteostasis and also contributes to the course of inflammatory diseases such as cancer, diabetes, obesity, and neurodegenerative diseases. In addition, the UPR is instrumental in allergic contact dermatitis. This inflammatory skin disease, affecting 5–10% of the population, is caused by T cells recognizing low-molecular weight organic chemicals and metal ions. In this mini-review, we discuss the orchestration of inflammatory responses by the interplay of the innate immune system with cellular stress responses in allergic contact dermatitis, with a focus on the UPR.     

脂肪细胞内质网应激反应蛋白与肥胖的关系

肥胖是2型糖尿病、冠心病、高脂血症、非酒精性脂肪肝等多种慢性疾病的基础病,属于代谢综合征类疾病。肥胖与内质网应激(Endoplasmic reticulum stress,ERS)和脂肪组织中未折叠蛋白反应(unfolded protein response,UPR)的激活有关[1]。近来国内外对应激反应蛋白在脂肪细胞ERS反应中的作用机制进行了大量的研究。     

ATM deficiency induces oxidative stress and endoplasmic reticulum stress in astrocytes

ATM kinase, the product of the ataxia telangiectasia mutated (Atm) gene, is activated by genomic damage. ATM plays a crucial role in cell growth and development. Here we report that primary astrocytes isolated from ATM-deficient mice grow slowly, become senescent, and die in culture. However, before reaching senescence, these primary Atm(-/-) astrocytes, like Atm(-/-) lymphocytes, show increased spontaneous DNA synthesis. These astrocytes also show markers of oxidative stress and endoplasmic reticulum (ER) stress, including increased levels of heat shock proteins (HSP70 and GRP78), malondialdehyde adducts, Cu/Zn superoxide dismutase, procaspase 12 cleavage, and redox-sensitive phosphorylation of extracellular signal-regulated protein kinase 1 and 2 (ERK1/2). In addition, HSP70 and ERK1/2 phosphorylation are upregulated in the cerebella of ATM-deficient mice. This increase in ERK1/2 phosphorylation is seen primarily in cerebellar astrocytes, or Bergmann glia, near degenerating Purkinje cells. ERK1/2 activation and astrogliosis are also found in other parts of the brain, for example, the cortex. We conclude that ATM deficiency induces intrinsic growth defects, oxidative stress, ER stress, and ERKs activation in astrocytes.