HIV感染中的细胞凋亡

CD4^ T细胞的丢失在HIV感染引起免疫缺陷过程中起着重要作用。但造成CD4^ T细胞丢失的具体机制还不清楚,细胞凋亡可能是CD4^ T细胞丢失的一个重要因素,HIV感染以后,病毒蛋白的持续性产出导致免疫系统的持续性激活,引起Th1细胞的丢失,Th1细胞通过合成Ⅰ型细胞因子,抑制淋巴细胞的自发凋亡,另外,病毒蛋白或其他因素能够使CD4^ ,CD8^ T细胞和APC转化为凋亡的效应细胞,通过Fas/FasL或其他途径引起细胞凋亡,HIV感染人体后凋亡细胞不仅有CD4^ T细胞,还包括B细胞,NK细胞,粒细胞,神经细胞和单细胞,凋亡作为机体的自我防护措施,在清除感染细胞的同时,并没有抑制HIV在单细胞/巨噬细胞内的复制,反而造成大量未感染细胞的凋亡,导致对HIV复制的失控,发展为严重的免疫缺陷,引起AIDS相关的机会性感染。     

一氧化氮介导细胞凋亡的分子基础

一氧化氮作为细胞内生物信使或细胞毒性分子介导细胞凋亡。阐述一氧化氮启动细胞凋亡与抑制细胞凋亡的复杂分子机制。     

细胞凋亡与病毒性肝炎

细胞凋亡（ａｐｏｐｔｏｓｉｓ）,是细胞在基因活动指导下的主动性死亡。细胞凋亡为普遍存在的一种生物现象,贯穿于机体整个生命活动过程的基本生理机制,调节着机体细胞增殖与更新间的平衡,维持组织器官正常生理功能及细胞数量的稳定。某些致病因子可以使细胞凋亡的基...     

病毒感染与细胞凋亡

本文叙述了ＥＢ病毒、甲级病毒、单纯疱疹病毒１型（ＨＳＶ－１）、牛痘病毒、腺病毒、人类免疫缺陷病毒（ＨＩＶ）和杆状病毒等感染细胞后对宿主细胞凋亡的影响,初步探讨了可能的机制,并作了展望。     

HIV Vpr蛋白诱导细胞凋亡研究进展

Vpr蛋白是HIV的一个辅助蛋白,可以诱导多种细胞的凋亡。目前的研究表明Vpr蛋白引起细胞凋亡主要是通过线粒体途径实现的。Vpr蛋白通过直接而且特异地与结合在PTPC中的ANT相互作用,改变线粒体膜通透性,导致凋亡诱导因子(AIF)和细胞色素C的释放,激活Caspase、DNases等的级联反应,引起核染色质的固缩,最终引起细胞凋亡。     

DFF和CIDE介导细胞凋亡的分子机制

DNA裂解因子（DFF）是由分子量分别为45kD和40kD两个亚单位组成的异源二聚体。在细胞凋亡信号启动的caspase级联活化过程中作为下游caspase的底物被活化并形成脱氧核糖核酸酶（DNase)。从而介导并调节DNA断裂和染色质凝聚,DFF作为细胞凋亡信号传递的主要途径在细胞凋亡中起着关键作用。诱导细胞死亡的DFF45样效应因子（CIDE）是与DFF同源的诱导凋亡因子,CIDE与DFF在结构,功能和作用上有很大的相似性,可发挥诱导凋亡的作用。本阐述了DFF和CIDE在诱导细胞凋亡过程中担当的角色和它们相互作用的机制。从而揭示DFF和CIDE在细胞凋亡过程中作为传递凋亡信号-caspase级联反应的下游因子在诱导凋亡时所处的关键地位和重要功能。     

人类免疫缺陷病毒与细胞凋亡

人类免疫缺陷病毒1型(HIV-1)感染可使被感染者体内CD4细胞数量减少,最终导致艾滋病。关于HIV-1如何杀死免疫细胞的精确机制仍是1个争论的问题。现已知道,细胞凋亡为HIV-1诱导细胞死亡的一个重要机制。HIV可直接诱导细胞凋亡,也可以通过活化作用,同源被感染的细胞的介导,以及CD^8 T细胞诱导细胞凋亡。且细胞因子在HIV诱导细胞凋亡的过程中发挥着重要的作用。本综述主要从以上几个方面总结HIV-1诱导细胞凋亡的机制。     

c—Myc和细胞凋亡

c-myc的表达产物c-Myc可诱导细胞凋 亡。c-Myc诱导的细胞凋亡发生在细胞周期的不同时期,并与细胞的种类、细胞的生长条件以及引起c-Myc不当表达的原因等相关。c-Myc起介导凋亡的作用,可能主要影响凋亡的起动。c-Myc先和Max结合形成异二聚体Myc-Max,再经Myc-Max和DNA结合控制诱导凋亡所需要的转录而对凋亡进行调控。c-Myc诱导凋亡的方式有“矛盾模型”和“双重信号模型”。另外,还受p53和ROS等的影响。     

内质网应激介导的细胞凋亡

内质网是细胞内重要的细胞器,内质网功能的损伤引起ER应激(ERS).内质网通过激活未折叠蛋白质反应(UPR)以保护由内质网应激所引起的细胞损伤,恢复细胞功能,包括暂停早期蛋白质合成、内质网分子伴侣和折叠酶的转录激活、内质网相关性降解(ERAD)的诱导.长期过强的内质网应激诱导内质网相关性细胞凋亡,清除受损细胞,包括内质网应激诱导CHOP/GADD153表达、JNK的激活以及caspase-12蛋白水解酶的活化等一系列生物学效应.     

几种免疫分子对Fas介导细胞凋亡的调节

Fas/APO-1介导的细胞凋亡在免疫自稳,免疫调控,免疫逃逸,免疫赦免等各个免疫生理,病理过程中均发挥着至关重要的作用。它可使免疫细胞的活化增殖和机体的免疫应答维持在一定的限度,从而避免发生过度免疫反应损伤机体。使机体的免疫系统处于一平衡状态。免疫分子。凋亡基因及抗凋亡基因表达的蛋白,以及多种药物均可调节Fas介导的细胞凋亡。本主要对几种免疫分子对Fas介导细胞凋亡的调节机制的研究进展做一论述。     

Apoptosis induced by granzyme B

Results of biochemical studies of apoptosis reactions induced by granzyme B are considered and summarized. Special attention is paid to the reactions of procaspase activation and limited proteolysis of apoptotic targets. Found values of kinetic constants of granzyme B-mediated enzymatic reactions are listed.     

HIV gp120 induced gene expression signatures in vaginal epithelial cells

Gp120 is the envelope protein of HIV which binds to CD4 independent proteins on vaginal epithelial cells. HIV-gp120 has been reported to modulate gene expression in several cell types. How this interaction may alter the physiologic vaginal milieu during the earliest stages of vaginal transmission of HIV, is currently unknown. Vaginal epithelial cells were treated with HIV-gp120, and a global snapshot of changes in gene expression profiles, were unraveled by microarray analysis. The differentially expressed genes were involved in diverse cellular functions. Genes of immunomodulatory processes and induction of proteases were highly enriched. We propose that the induction of inflammation and proteases may act in concert to weaken the vaginal epithelium, making it more permeable to viral entry. Identification of the gene signatures involved in vaginal-HIV dialogue would aid in understanding the environ induced by HIV itself, as the virus invades and gains entry into its host.     

GBV-C/HIV共感染对AIDS疾病进程和HIV病毒复制的影响

近年来,一些研究发现,GBV-C/HIV共感染可延缓HIV感染疾病的进程,然而也有一些研究得出不同的结论.本研究收集我国安徽省阜阳市HIV血清学阳性的既往献血员血浆标本,对其进行GBV-C感染的检测,研究GBV-C/HIV共感染与HIV病毒载量和CD4 T淋巴细胞绝对计数的关系.用RT-PCR和酶联免疫法检测,在203人中检出GBV-C感染52例,显示该人群GBV-C的感染率为25.6%,男性感染者(35例,67.3%)高于女性感染者(17例,32.7%).分析发现,GBV-C感染与未感染两组患者的CD4 T淋巴细胞绝对计数和HIV病毒载量数据均无统计学差异.本研究中的HIV-1感染者均未接受ART治疗,因而排除了治疗对疾病进展的影响.研究结果显示,在HIV-1感染晚期的献血人群,GBV-C/HIV共感染对CD4细胞和病毒复制水平无显著影响.由于本研究对象中无HIV-1早期感染者,因而不能判断GBV-C在HIV-1感染的早期对疾病进展有无影响.     

Tunneling nanotubes (TNT) are induced by HIV-infection of macrophages: a potential mechanism for intercellular HIV trafficking

Cell to cell communication is essential for the organization/coordination of multicellular systems and cellular development. Cellular communication is mediated by soluble factors, including growth factors, neurotransmitters, cytokines/chemokines, gap junctions, and the recently described tunneling nanotubes (TNT). TNT are long cytoplasmatic bridges that enable long range directed communication between cells. The proposed function for TNT is the cell-to-cell transfer of large cellular structures such as vesicles and organelles. We demonstrate that HIV-infection of human macrophages results in an increased number of TNT, and show HIV particles within these structures. We propose that HIV “highjacks” TNT communication to spread HIV through an intercellular route between communicated cells, contributing to the pathogenesis of AIDS.     

Apoptosis induced by high- and low-LET radiations

Cell death after irradiation occurs by apoptosis in certain cell populations in tissues. The phenomenon also occurs after high linear energy transfer (LET) irradiation, and the relative biological effectiveness (RBE) is 3 to 4 (with respect to low-LET radiation and apoptosis in intestinal crypts) for neutrons with energies of 14 MeV and up to 600 MeV. It is thought thatp53 plays a role in the phenomenon, as radiation-induced apoptosis is not observed inp53-null animals.     

Apoptosis induced by inhibition of intercellular contact

The LIM 1863 colon carcinoma cell line grows as structural organoids of goblet and columnar cells around a central lumen and provides a model for the development of stem cells in the normal colon. The organoid structure can be disrupted by removal of calcium from the medium, resulting in a suspension of single cells. Upon readdition of calcium, the cells reform the organoid structure over a period of 24 h, and ultrastructural examination of the reforming cells reveals that this involves a complex process that we have termed clutching. To determine the adhesion molecules involved in organoid formation we attempted to block this process by single cell suspensions of LIM 1863 reseeded in the presence of monoclonal antibodies. An anti-integrin antibody directed against a conformational epitope on the alpha v subunit totally inhibited organoid reformation. As a consequence of this inhibition of cell contact the colon carcinoma cells rapidly underwent apoptosis. Investigations of the apoptotic pathway involved suggested an induction mechanism since the onset of apoptosis in the contact- inhibited cells showed specific increased synthesis of 68- and 72-kD proteins. In addition, immunoblotting of cytosolic and nuclear extracts of the cells revealed the rapid translocation of the tumor suppressor gene product, p53 to the cell nucleus upon induction of apoptosis. These results suggest that cell-cell adhesion may be a vital regulator of colon development overcome in tumor cells by loss of adhesion molecules or of functional p53 protein.     

应用RD-PCR技术制备HIV基因芯片探针

利用限制性显示 (RD PCR)技术快速分离HIV 1基因片段制备DNA芯片探针 .以Sau3AⅠ酶切HIV基因 ,得到许多大小适合芯片的限制性酶切片段 .然后在片段两端接上接头 ,根据酶切位点、接头的序列设计通用引物 .在该通用引物的 3′端分别延伸一个碱基后 ,通过引物间的两两组合 ,将PCR反应分成 10个亚组 .纯化各组PCR产物 ,克隆到T载体上 .阳性克隆经鉴定、扩大培养后提取质粒 .以质粒为模板扩增靶片段并进行序列分析 .每个亚型得到了十几个 10 0～ 10 0 0bp的HIV基因片段 .研究表明 ,RD PCR技术是一种有效的快速制备基因芯片探针的方法