病毒基因与细胞凋亡

细胞凋亡是受遗传控制的细胞自灭过程,是机体维持稳态的主要机制之一。是一种典形的细胞程序化死亡,细胞程序化死亡的诱导与调控机制是当今生物学中非常活跃的研究领域,涉及到细胞生物学、病毒学、免疫学,发育生物学,致癌生物学等学科,具有重要的理论与实践意义。引起细胞凋亡的因素很多,本文仅就病毒基因与细胞凋亡的关系,主要以疱疹病毒科,腺病毒科,杆状病毒科和逆转录病毒中某些病毒与细胞凋亡相关的基因及其结构,作用     

TNF受体家庭介导的细胞凋亡信号转导

肿瘤坏死因子（ＴＮＦ）家庭是一类多功能的细胞因子,具有诱导细胞凋亡、抗病毒、免疫调节等多种生物学活性,其中一些成员可以通过和细胞膜上相应受体结合,启动细胞内的凋亡机制,而诱导细胞凋亡,一些蛋白质（如ＴＲＡＤＤ、ＦＡＤＤ、ＲＩＰ、ＲＡＩＤＤ等）参与这些信号传递过程,越来赵多的ＴＮＦ家庭成员,ＴＮＦ受体以及与细胞凋亡相产在的Ｃａｓｐａｓｅ蛋白酶２成员被人们发现。     

Alzheimer病与细胞凋亡

Ａｌｚｈｅｉｍｅｒ病（简称ＡＤ）是一种老年期痴呆综合征,其病因及发病机制尚不十分清楚。近年来的研究表明,细胞凋亡（ａｐｏｐｔｏｓｉｓ）参与了ＡＤ神经元退行性病变。探讨细胞凋亡与ＡＤ的关系对深入了解ＡＤ的发病机制及研究其防治均有重要意义。１．细胞凋亡在...     

调节细胞凋亡的新成员——ICE

调节细胞凋亡的新成员──ＩＣＥ阎水忠,吴旻（中国医学科学院,中国协和医科大学肿瘤研究所分子肿瘤学国家重点实验室,北京１０００２１）关键词细胞凋亡,ＩＬ－１β转换酶细胞凋亡（ａｐｏｐｔｏｓｉｓ）的研究近年来成为包括发育学、细胞生物学以及肿瘤学等多种学科...     

细胞凋亡生化通路的发现者--记华裔科学家王晓东

细胞凋亡（apoptosis）,又被称为细胞程序化死亡（programmed cell death,PCD）,是多细胞生物通过主动方式杀死不需要细胞的一种方式。相对于细胞坏死（necrosis）,细胞凋亡采取一种有序的方式,是生物发育过程中特定细胞消除的一种重要方式。从20世纪70年代开始,许多生物学家开始研究它的机制,经过30多年的研究,现在已经成为当前生命科学三大热点之一,特别是2002年3位科学家还由于在这方面的贡献而获得了诺贝尔生理与医学奖。     

前凋亡因子与脑血管疾病的关系研究

Bim（bcl—2 interacting mediator of cell death）,又称前凋亡因子（pro-apoptotic Bcl-2 proteins）,是Bcl-2家族中BH3-only亚家族成员,具有促凋亡活性,是重要的凋亡诱导基因,在细胞凋亡过程中有重要作用,而最近研究表明凋亡是脑缺血后神经元死亡的重要形式,故Bim与脑血管疾病关系密切。本文就Bim的分子结构、生物学功能及其调节机制作一简单阐述,并重点讨论了其与脑血管疾病关系方面的研究进展,以望为脑血管疾病的防治提供一新的途径。     

受体相互作用蛋白3——细胞凋亡与坏死的调节阀

综述了受体相互作用蛋白(RIPs)蛋白结构和RIP3调控细胞凋亡与坏死机制的研究进展．受体相互作用蛋白3(receptor-interacting protein 3, RIP3)是丝/苏氨酸蛋白激酶家族成员之一,该蛋白质家族包含一类高度保守的丝/苏氨酸激酶结构域．RIP家族激酶作为细胞应激传感分子,在调控细胞凋亡、细胞坏死和存活通路中发挥重要作用．近年发现,RIP3参与肿瘤坏死因子TNFα诱导的细胞程序化坏死的生物学过程．认识RIP3调控TNFα诱导的细胞凋亡与坏死不同死亡途径转换的分子机制,有助于发现肿瘤治疗的新策略．     

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...     

细胞凋亡的结构生物学研究进展

在多细胞生物体内,细胞会发生编程性死亡(即细胞凋亡),使得细胞数量得到精确调控。细胞凋亡调控的异常与癌症、自身免疫病、神经退行性疾病等疾病密切相关。在过去的二十年里,人们详细地研究了参与细胞凋亡调控的分子机制。该文综述了近年来利用结构生物学手段,对参与细胞凋亡调控的分子,主要是Caspase和与Caspase活性调控直接相关的蛋白功能的研究进展。     

常规组织切片凋亡细胞原位末端标记方法

凋亡是有别于组织坏死的一种细胞死亡方式,多与基因调控的编程性死亡有关。准确地判断细胞凋亡对探讨程序化细胞死亡诱发机制具有重要意义。本文采用Biotin-16-dUTP对凋亡细胞内DNA断裂片段的末端进行标记,可原位检测常规组织切片上的凋亡细胞,方法具有敏感、直观、重复性好等优点。     

Mechanisms of Procaspase-8 Activation in the Extrinsic Programmed Cell Death Pathway

Molecular Biology - Caspase-8 performs initiatory functions during the induction of apoptosis through the extrinsic pathway. Apoptosis is a type of programmed cell death that plays an important...     

杆状病毒凋亡抑制基因的研究进展

杆状病毒(bacu lovirus)感染昆虫细胞能引起细胞凋亡,但在长期进化过程中,杆状病毒可通过自身编码凋亡抑制基因的表达,抑制细胞凋亡以利于自己的增殖。目前在杆状病毒基因组中已发现两种不同类型的细胞凋亡抑制基因p35/p49和iap,这两类凋亡抑制基因分别作用于细胞凋亡途径的不同位点,以抑制细胞的凋亡。近年来人们对这两种基因的蛋白结构及作用机制等方面进行了大量的研究,这些为今后研究昆虫细胞凋亡,扩大杆状病毒宿主范围等方面奠定了基础。     

Herpes Simplex Virus Inhibits Apoptosis through the Action of Two Genes, Us5 and Us3

Apoptosis of virus-infected cells occurs either as a direct response to viral infection or upon recognition of infection by the host immune response. Apoptosis reduces production of new virus from these cells, and therefore viruses have evolved inhibitory mechanisms. We previously showed that laboratory strains of herpes simplex virus type 1 (HSV-1) protect infected cells from apoptosis induced by cytotoxic T lymphocytes or ethanol. We have now evaluated the ability of HSV-1 and HSV-2 laboratory and clinical isolates to inhibit apoptosis induced by anti-Fas antibody or UV irradiation and explored the genetic basis for this inhibition. HSV-1 isolates inhibited apoptosis induced by UV or anti-Fas antibody. In contrast, HSV-2 clinical isolates failed to inhibit apoptosis induced by either stimulus, although the HSV-2 laboratory strain 333 had a partial inhibitory effect on UV-induced apoptosis. Inhibition of apoptosis by HSV was accompanied by marked reduction of caspase-3 and caspase-8 activity. Deletion of the HSV-1 Us3 gene markedly reduced inhibition of UV-induced apoptosis and partially abrogated inhibition of Fas-mediated apoptosis. Conversely, deletion of the HSV-1 Us5 gene markedly reduced protection from Fas-mediated apoptosis and partially abrogated protection from UV. The Us11 and Us12 genes were not necessary for protection from apoptosis induced by either stimulus. The differences between HSV-1 and HSV-2 in the ability to inhibit apoptosis may be factors in the immunobiology of HSV infections.     

Epstein-Barr virus provides a new paradigm: a requirement for the immediate inhibition of apoptosis

DNA viruses such as herpesviruses are known to encode homologs of cellular antiapoptotic viral Bcl-2 proteins (vBcl-2s), which protect the virus from apoptosis in its host cell during virus synthesis. Epstein-Barr virus (EBV), a human tumor virus and a prominent member of γ-herpesviruses, infects primary resting B lymphocytes to establish a latent infection and yield proliferating, growth-transformed B cells in vitro. In these cells, 11 viral genes that contribute to cellular transformation are consistently expressed. EBV also encodes two vBcl-2 genes whose roles are unclear. Here we show that the genetic inactivation of both vBcl-2 genes disabled EBV's ability to transform primary resting B lymphocytes. Primary B cells infected with a vBcl-2-negative virus did not enter the cell cycle and died of immediate apoptosis. Apoptosis was abrogated in infected cells in which vBcl-2 genes were maximally expressed within the first 24 h postinfection. During latent infection, however, the expression of vBcl-2 genes became undetectable. Thus, both vBcl-2 homologs are essential for initial cellular transformation but become dispensable once a latent infection is established. Because long-lived, latently infected memory B cells and EBV-associated B-cell lymphomas are derived from EBV-infected proapoptotic germinal center B cells, we conclude that vBcl-2 genes are essential for the initial evasion of apoptosis in cells in vivo in which the virus establishes a latent infection or causes cellular transformation or both.     

Detection and quantification of apoptosis in transiently transfected adherent cells.

Apoptosis is a highly conserved form of cell death present in all eukaryotic cell types and controlled by multiple genes. Several methods have been developed to quantify apoptosis, but none is adapted for all cell types. It is particularly difficult to reliably assay apoptosis of adherent cells. We describe a new, rapid and reliable flow cytometric method which can be used for quantifiying apoptosis in a sub-population of transiently transfected adherent cells. This technique is based on the detection of transfected cells and the apoptotic sub-population by immunofluorescence and Annexin-V labelling, respectively.     

Effects of manipulating apoptosis on Sindbis virus infection of Aedes aegypti mosquitoes

Improved control of vector-borne diseases requires an understanding of the molecular factors that determine vector competence. Apoptosis has been shown to play a role in defense against viruses in insects and mammals. Although some observations suggest a correlation between apoptosis and resistance to arboviruses in mosquitoes, there is no direct evidence tying apoptosis to arbovirus vector competence. To determine whether apoptosis can influence arbovirus replication in mosquitoes, we manipulated apoptosis in Aedes aegypti mosquitoes by silencing the expression of genes that either positively or negatively regulate apoptosis. Silencing of the A. aegypti anti-apoptotic gene iap1 (Aeiap1) caused apoptosis in midgut epithelium, alterations in midgut morphology, and 60 to 70% mosquito mortality. Mortality induced by Aeiap1 silencing was rescued by cosilencing the initiator caspase gene Aedronc, indicating that the mortality was due to apoptosis. When mosquitoes which had been injected with Aeiap1 double-stranded RNA (dsRNA) were orally infected with Sindbis virus (SINV), increased midgut infection and virus dissemination to other organs were observed. This increase in virus infection may have been due to the effects of widespread apoptosis on infection barriers or innate immunity. In contrast, silencing the expression of Aedronc, which would be expected to inhibit apoptosis, reduced SINV midgut infection and virus dissemination. Thus, our data suggest that some level of caspase activity and/or apoptosis may be necessary for efficient virus replication and dissemination in mosquitoes. This is the first study to directly test the roles of apoptosis and caspases in determining mosquito vector competence for arboviruses.     

Relevance of signaling molecules for apoptosis induction on influenza A virus replication

Apoptosis is an important mechanism to maintain homeostasis in mammals, and disruption of the apoptosis regulation mechanism triggers a range of diseases, such as cancer, autoimmune diseases, and developmental disorders. The severity of influenza A virus (IAV) infection is also closely related to dysfunction of apoptosis regulation. In the virus infected cells, the functions of various host cellular molecules involved in regulation of induction of apoptosis are modulated by IAV proteins to enable effective virus replication. The modulation of the intracellular signaling pathway inducing apoptosis by the IAV infection also affects extracellular mechanisms controlling apoptosis, and triggers abnormal host responses related to the disease severity of IAV infections. This review focuses on apoptosis related molecules involved in IAV replication and pathogenicity, the strategy of the virus propagation through the regulation of apoptosis is also discussed.     

A microarray analysis of genes involved in relating egg production to nutritional intake in Drosophila melanogaster

Egg chambers of Drosophila are reabsorbed under conditions of nutritional shortage by inducing apoptosis at stages 8 and 9, midway through oogenesis. Nutritional shortage leads to an increase in ecdysone concentration in flies. Apoptosis at stage 8/9 is also induced by 20-hydroxyecdysone injection into the females maintained with adequate nutrition. The expression pattern in the ovary of some ecdysone response genes, E75A, BR-C, is different according to the nutritional environment and the overexpression of these genes induces apoptosis. Apoptosis is suppressed by Juvenile hormone analog treatment of females under nutritional shortage. We predict nutritional and stress response genes control hormone levels and the increase in ecdysone concentration in the flies following starvation induces the ovarian apoptosis. We therefore used a microarray approach to identify the genes involved in receiving the nutritional signal from the environment and translating it in the ovary, thus initiating and executing apoptosis.     

Genetic control of programmed cell death in Drosophila melanogaster

Apoptosis is a genetically controlled form of cell death that is an important feature of animal development and homeostasis. The genes involved in the control and execution of apoptosis are conserved throughout evolution. However, the actual molecular mechanisms used by these genes vary from species to species. In this review, we focus on the genetic components of apoptosis in the fruit fly Drosophila melanogaster, and compare their mode of action to the one employed by the homologous genes in mammals. We also cover recent advances that show that apoptotic genes have a requirement in processes other than apoptosis.     

Murine cytomegalovirus m41 open reading frame encodes a Golgi-localized antiapoptotic protein

Viruses have evolved various strategies to prevent premature apoptosis of infected host cells. Some of the viral genes mediating antiapoptotic functions have been identified by their homology to cellular genes, but others are structurally unrelated to genes of known function. In this study, we used a random, unbiased approach to identify such genes in the murine cytomegalovirus genome. From a library of random transposon insertion mutants, a mutant virus that caused premature cell death was isolated. The transposon was inserted within open reading frame m41. An independently constructed m41 deletion mutant showed the same phenotype, whereas deletion mutants lacking the adjacent genes m40 and M42 did not. Apoptosis occurred in different cell types, could be blocked by caspase inhibitors, and did not require p53. Within the murine cytomegalovirus genome, m41, m40, and m39 form a small cluster of genes of unknown function. They are homologous to r41, r40, and r39 of rat cytomegalovirus, but lack sequence homology to UL41, UL40, and UL37 exon 1 (UL37x1) which are located at the corresponding positions of the human cytomegalovirus genome. Unlike UL37x1 of human cytomegalovirus, which encodes a mitochondrion-localized inhibitor of apoptosis that is essential for virus replication, m41 encodes a protein that localizes to the Golgi apparatus. The murine cytomegalovirus m41 product is the first example of a Golgi-localized protein that prevents premature apoptosis and thus extends the life span of infected cells.