细胞凋亡与肿瘤

在进化过程中,生物体内形成了一系列调节机制,用以对细胞的分裂、分化、以及细胞的存亡进行精细的调节和严密的控制。在具有自我更新能力的组织中,存在着有丝分裂产生细胞的计划性死亡丧失细胞之间的微妙平衡,使体内各种细胞的数量和功能处于相对恒定的状态。细胞凋亡(Apoptosis),也称程序性细胞死亡(Programmed CellDeath,PCD),是细胞接收某种信号或受到某些因素刺激后一种主动的,由一些凋亡相关基因相互作用的细胞消亡过程。发生凋亡的细胞体积缩小,染色质浓缩,细胞骨架解体,细胞膜出现发泡现象,形成膜包裹的凋亡小体。DNA双链在染色体间隔处逐渐断裂,形成一系列长度不同的梯度片断。     

细胞凋亡对衰老的调节在肿瘤的发生发展及治疗的研究进展

细胞凋亡是细胞死亡的一种形式,是调节机体正常发育的重要机制,涉及一系列在维持细胞自稳中发挥重要作用的调控因子.肿瘤的发生、发展与治疗也受到凋亡调控蛋白的调控,细胞凋亡也参与多种与衰老相关的病理过程,本研究就细胞凋亡通路及其对衰老及肿瘤的相关调控机制进行综述.     

细胞凋亡与NF-κB激活的信号传导研究

细胞凋亡是细胞受基因调控的主动死亡方式,对于生物体的正常发育及生理功能的维持具有重要意义。NF-κB是一类在动物细胞中广泛表达的转录因子,其主要生理功能之一是通过诱导凋亡抑制基因的转录,拮抗细胞凋亡的发生。NF-κB的活化调控是细胞生死抉择过程的关键机制之一。现已证明细胞凋亡及NF-κB活化的异常会导致多种人类疾病。本项目从凋亡的执行机制和调控机制两方面入手,对细胞凋亡的机理进行了研究。建立了基于爪蟾卵细胞提取物的非细胞凋亡诱导体系,并利用这一体系,发现爪蟾细胞凋亡特异核酸酶XAD及其特异性的抑制因子IXAD;首次证明磷酸肌酸和核质素在凋亡过程中的作用。克隆了3个新的凋亡诱导基因。在细胞凋亡的调节机制方面,克隆了7个分别作用于NF-κB活化信号通路不同步骤的新的调节基因,发现5个已知蛋白调节不同NF-κB活化途径的新功能。此外,在国际上较早开展了植物细胞凋亡的研究,首次报道体外培养植物细胞凋亡过程中有细胞色素C的释放。     

细胞凋亡的研究进展

1972年 ,Ｋｅｒｒ等首次提出细胞凋亡的概念。细胞凋亡 (ａｐｏｐｔｏｓｉｓ)是多细胞生物维持自身稳定 ,由基因控制的细胞自主的有序的死亡 ,又称为程序性细胞死亡 (ｐｒｏｇｒａｍｍｅｄｃｅｌｌｄｅａｔｈ ,ＰＣＤ)。机体通过细胞凋亡消除损伤、衰老与突变的细胞 ,以维持生理平衡 ,是一种主动的、有程序的细胞死亡过程。细胞凋亡的研究表明 ,它与胚胎发育、器官的发育与退化、免疫、造血、细胞群体稳定等生理过程有着极其重要的关系 ,并在ＡＩＤＳ、肿瘤的发生和治疗中起着重要作用。因而 ,细胞凋亡的研究日益受到人们的关注 ,成为当今生…     

实验性肝损伤与细胞凋亡

对各种肝脏疾病发病机制的深入探讨与中西医治疗药物的筛选 ,在很大程度上依赖于和人类肝疾病病理机制相似的实验动物模型的建立与应用[1] 。细胞凋亡 (ａｐｏｐｔｏｓｉｓ)是细胞死亡的形式之一 ,亦称程序性死亡 (ｐｒｏｇｒａｍｍｅｄｃｅｌｌｄｅａｔｈ) ,由于其特殊的生物学意义而逐步成为一个新的研究热点。近年来的研究表明 ,细胞凋亡在肝细胞损伤中发挥着重要的作用。本文综述了凋亡机制在几种常见重要的实验性肝损伤作用的研究进展。1　ＣｏｎＡ性肝损伤与细胞凋亡1992年Ｔｉｅｇｓ等[2 ] 成功地应用ＣｏｎＡ(Ｃｏｎｃａｎａｖａｌ …     

双酚A暴露致神经细胞凋亡和炎症性死亡的研究进展

双酚A(BPA)是生产聚碳酸酯和环氧树脂塑料的添加剂,具有内分泌干扰物效应。由于大量研究发现BPA具有神经毒性,其暴露对大脑神经功能及行为变化的影响受到越来越多的关注.研究发现,氧化应激常伴随着BPA诱导的神经细胞凋亡和炎症性死亡(焦亡)反应的发生,导致神经细胞形态和功能改变,是BPA暴露与神经系统疾病相关性的重要连接纽带.研究聚焦BPA暴露诱导神经细胞凋亡和炎症性死亡这一生理现象,对BPA暴露通过线粒体、内质网以及死亡受体通路信号上的细胞凋亡的分子作用机制的详细介绍,探讨了细胞凋亡、细胞焦亡之间的关系以及他们与神经系统疾病的潜在关系,指出BPA暴露诱导的神经细胞凋亡与炎性反应的分子机制尚需要大量的动物、靶向敲除实验以及人群实验加以验证.同时,应关注低剂量BPA暴露参与毒性通路或与其他毒性通路相互作用而加重复合污染物暴露的健康效应,为深入研究BPA暴露的神经毒性机制及其毒性干预提供参考.     

浅析内质网与细胞凋亡

内质网(endoplasmic reticulum,ER)在细胞内分布广泛,是最大的细胞器,主要负责蛋白质的合成转运、信号肽识别、糖基化修饰等过程和钙离子的贮存,信号转导及细胞内钙的再分布。细胞凋亡是诱导性细胞自杀过程,主要由线粒体介导。近来研究发现过度内质网应激可启动细胞凋亡,是一条新的细胞凋亡信号传导通路,这一信号传导通路包括非折叠蛋白反应和钙离子起始信号等机制,并且,由内质网应激特异性激活Caspase-12而最终导致细胞凋亡。本文对该凋亡途径的研究进展作了简要综述。     

维管植物导管元素分化与细胞程序性死亡

通过遗传控制的细胞死亡是植物正常生长和发育的重要过程，是近年来国内外的研究热点之一。维管植物的导管和筛管由死亡的管导分子组成，本文着重讨论了维管植物的导分子形成过程中的细胞程序性死亡（ｐｒｏｇｒａｍｍｅｄ ｃｅｌｌｄｅａｔｈＰＣＤ）的形态和化特性以及参与找在因，并介绍了植物生长发育过程中ＰＣＤ存在的时空广泛性。虽然植物发育生殖过程中的ＰＣＤ与动物细胞通过遗控制的细胞死亡是植物正常生长和发育的重要过程，是近年来国内外的研究热点之一，维管植物的导管和筛管由天文馆的导管分子组成。本文着重讨论了维管植物的导管分子形成过程中的细程序性死亡（programmed cell death PCD)的形态和生化特征以及参与的基因，并介绍了植物生长发育过程中ＰＣＤ存在的时空广泛性。虽然植物发育和生殖过程中的ＰＣＤ与动物细胞凋亡存在许多相似的形太必生化特征，但细胞通过自溶或自自我吞噬来死亡，而并不形成动物细胞凋亡中典型的凋亡小体。说明这些ＰＣＤ类型本质上凋亡型ＰＣＤ。导管分子的死亡是一种典型的植物ＰＣＤ。近年来体外系统研究表明，导管元素分析中的细胞死亡程序与动物细胞凋亡不同。     

线粒体外膜通道蛋白VDAC与靶向肿瘤细胞凋亡

VDAC(Voltage-dependent anion channel)是位于线粒体外膜上的一种主要通道蛋白,参与线粒体内外物质和能量的运输,在线粒体与细胞其它部位的通讯中起重要调节作用.近年来研究发现,VDAC也是线粒体与其它蛋白质相互作用的功能结合位点,可与多种凋亡调节蛋白(如HK-Ⅰ/Ⅱ、Bcl-2家族蛋白、tubulin、MAP2/4等)以及非蛋白调节因子相互作用,参与调控细胞凋亡.因此,VDAC成为线粒体凋亡通路中一种关键的靶蛋白.本文对近年来VDAC在肿瘤细胞凋亡中的作用机制进行简要综述.     

溶酶体蛋白酶cathepsin B参与介导前列腺癌PC-3细胞凋亡

细胞凋亡是多细胞生物清除多余、损伤或有潜在危险细胞的一种主要生理机制.蛋白水解酶是细胞凋亡研究的重要对象,其中大部分工作都集中在探索caspases的功能和调控上.近年来,越来越多的证据显示一些非caspases蛋白酶如位于溶酶体中的cathepsins特别是cathepsin B(CTSB)参与细胞凋亡过程.溶酶体cathepsins既可以与caspases协同作用,也可以不依赖于caspases独立执行凋亡功能.选取人前列腺癌PC-3细胞株作为研究对象,通过检测PC-3细胞对TNFα、D-sphingosine两种凋亡诱导剂和caspases、cathepsins抑制剂的应答反应,以及细胞凋亡过程中溶酶体、线粒体的结构变化,证实了D-sphingosine引起PC-3细胞死亡的效应主要通过释放溶酶体中蛋白酶CTSB实现,CTSB和caspases均参与介导TNFα诱导的PC-3细胞凋亡过程,并且很可能在不同的凋亡信号通路中发挥作用.     

Programmed cell death, mitochondria and the plant hypersensitive response.

The plant response to attempted infection by microbial pathogens is often accompanied by rapid cell death in and around the initial infection site, a reaction known as the hypersensitive response. This response is associated with restricted pathogen growth and represents a form of programmed cell death (PCD). Recent pharmacological and molecular studies have provided functional evidence for the conservation of some of the basic regulatory mechanisms underlying the response to pathogens and the activation of PCD in animal and plant systems. In animals, the mitochondrion integrates diverse cellular stress signals and initiates the death execution pathway, and studies indicate a similar involvement for mitochondria in regulating PCD in plants. But many of the cell-death regulators that have been characterized in humans, worms and flies are absent from the Arabidopsis genome, indicating that plants probably use other regulators to control this process.     

Timing of plant immune responses by a central circadian regulator

The principal immune mechanism against biotrophic pathogens in plants is the resistance (R)-gene-mediated defence. It was proposed to share components with the broad-spectrum basal defence machinery. However, the underlying molecular mechanism is largely unknown. Here we report the identification of novel genes involved in R-gene-mediated resistance against downy mildew in Arabidopsis and their regulatory control by the circadian regulator, CIRCADIAN CLOCK-ASSOCIATED 1 (CCA1). Numerical clustering based on phenotypes of these gene mutants revealed that programmed cell death (PCD) is the major contributor to resistance. Mutants compromised in the R-gene-mediated PCD were also defective in basal resistance, establishing an interconnection between these two distinct defence mechanisms. Surprisingly, we found that these new defence genes are under circadian control by CCA1, allowing plants to 'anticipate' infection at dawn when the pathogen normally disperses the spores and time immune responses according to the perception of different pathogenic signals upon infection. Temporal control of the defence genes by CCA1 differentiates their involvement in basal and R-gene-mediated defence. Our study has revealed a key functional link between the circadian clock and plant immunity.     

植物生殖与胚胎发育过程中的细胞程序性死亡

生殖与胚胎发育过程中植物细胞程序性死亡（ＰＣＤ）的典型特点在于它的细胞类型特异性。即在特定时期，只有特定的细胞才会发生ＰＣＤ。介绍了植物生殖和胚胎发育过程中各种类型的细胞在特定时期所发生的ＰＣＤ的形态和生化特征。这些ＰＣＤ类型包括大小孢子的退化、单性花的形成、性别决定、心皮通化、花粉发育及绒毡层的解体、胚胎发育过程中胚柄及糊粉层的消失以及体细胞胚胎发生等。同时对植物生长和发育过程中ＰＣＤ的作用及其     

植物细胞程序性死亡的研究进展

细胞程序性死亡是在植物体的一定发育阶段普遍发生的受特定基因调控的自然的细胞死亡过程.本文就植物PCD的一般特征、普遍性及其机理等方面的研究进展进行综述.     

Identification of pathways regulating cell size and cell-cycle progression by RNAi

Many high-throughput loss-of-function analyses of the eukaryotic cell cycle have relied on the unicellular yeast species Saccharomyces cerevisiae and Schizosaccharomyces pombe. In multicellular organisms, however, additional control mechanisms regulate the cell cycle to specify the size of the organism and its constituent organs. To identify such genes, here we analysed the effect of the loss of function of 70% of Drosophila genes (including 90% of genes conserved in human) on cell-cycle progression of S2 cells using flow cytometry. To address redundancy, we also targeted genes involved in protein phosphorylation simultaneously with their homologues. We identify genes that control cell size, cytokinesis, cell death and/or apoptosis, and the G1 and G2/M phases of the cell cycle. Classification of the genes into pathways by unsupervised hierarchical clustering on the basis of these phenotypes shows that, in addition to classical regulatory mechanisms such as Myc/Max, Cyclin/Cdk and E2F, cell-cycle progression in S2 cells is controlled by vesicular and nuclear transport proteins, COP9 signalosome activity and four extracellular-signal-regulated pathways (Wnt, p38betaMAPK, FRAP/TOR and JAK/STAT). In addition, by simultaneously analysing several phenotypes, we identify a translational regulator, eIF-3p66, that specifically affects the Cyclin/Cdk pathway activity.     

植物细胞程序性死亡研究进展

植物细胞程序性死亡普遍存在于植物生长发育及环境相互作用过程中,是由基因调控的、主动的细胞死亡过程。植物PCD已成为当前生物学研究的热点之一。本文概述了植物细胞程序性死亡的形态学、分子生物学特征以及植物PCD在植物发育、环境胁迫、超敏反应中的存在,并就植物PCD的细胞形态学、分子生物学等检测方法以及植物PCD的基因、酶和信号分子的调控进行了综述。     

Domain structure of human glucocorticoid receptor and its relationship to the v-erb-A oncogene product

The interaction of steroids with their nuclear receptors induces a cascade of regulatory events that results from the activation of specific sets of genes by the hormone/receptor complex. Steroids, either acting alone or possibly synergistically with other growth factors, can influence the DNA synthesis and proliferation of specific target cells, initiate developmental pathways and activate expression of the differentiated phenotype. Moreover, steroid hormones have been implicated in abnormal growth regulation both in tumours and tumour-derived cell lines. The identification of complementary DNAs encoding the human glucocorticoid receptor (hGR) predicts two protein forms (alpha and beta; 777 and 742 amino acids long, respectively) which differ at their carboxy termini. We report here that both forms of the receptor are related, with respect to their domain structure, to the v-erb-A oncogene product of avian erythroblastosis virus (AEV), which suggests that steroid receptor genes and the c-erb-A proto-oncogene are derived from a common primordial regulatory gene. Therefore, oncogenicity by AEV may result, in part, from the inappropriate activity of a truncated steroid receptor or a related regulatory molecule encoded by v-erb-A. This suggests a mechanism by which transacting factors may facilitate transformation. We also identify a short region of hGR that is homologous with the Drosophila homoeotic proteins encoded by Antennapedia and fushi tarazu.     

细胞编程性死亡及其生物学意义

细胞编程性死亡(英文编写为PCD)是多细胞生物的自然属性,它按照一定的基因编码在时空上顺次表达使死亡细胞呈现一定的表观现象及生理生化特征。PCD受来自机体内其它细胞信号等内源性因素和药物、物理等外源性因素的调节。PCD是一种主动死亡方式且表现为单细胞性,与病理因素作用下的坏死不同,但又有一定联系。PCD在动、植物体的生长发育和成体新陈代谢中有重要的调节作用,PCD异常是某些疾病发病的重要原因     

Genetic pathways that regulate ageing in model organisms

Searches for genes involved in the ageing process have been made in genetically tractable model organisms such as yeast, the nematode Caenorhabditis elegans, Drosophila melanogaster fruitflies and mice. These genetic studies have established that ageing is indeed regulated by specific genes, and have allowed an analysis of the pathways involved, linking physiology, signal transduction and gene regulation. Intriguing similarities in the phenotypes of many of these mutants indicate that the mutations may also perturb regulatory systems that control ageing in higher organisms.