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1.
死亡不仅是所有细胞的最终命运,而且它与细胞分裂、增殖一样,在整个机体的生长、发育中具有不可替代的作用.目前认为,除了坏死外,细胞死亡形式分为程序性细胞死亡(programmedcell death,PCD),包括凋亡(apoptosis)和自噬(autophagy),及非程序性细胞死亡(non-programmedcell death,NPCD),包括副凋亡(paraptosis)、细胞有丝分裂灾难(mitotic catastrophe)和胀亡(oncosis)  相似文献   

2.
细胞是生物体最基本的结构单位和功能单位,细胞死亡对于多细胞生物的发育和稳态极为重要,也是生命的基本过程之一。目前认为细胞死亡形式主要分为两大类:非程序性细胞死亡(non-programmed cell death,NPCD)即坏死(necrosis);程序性细胞死亡(programmed cell death,PCD)。PCD与坏死不同,组织内无可见的炎症反应,无死亡细胞的溶解。程序性细胞死亡按其发生机制的不同可以分为凋亡(apoptosis)、自吞噬性程序性细胞死亡(autophagic cell death)、类凋亡/副凋亡(paraptosis)、细胞有丝分裂灾难(mitotic catastrophe)、胀亡(oncosis)、焦亡(pyroptosis)、胞质自切(autoschizis)、细胞程序性坏死(necroptosis)、细胞侵入性死亡(entosis)、铁死亡(ferroptosis)等。近年来,程序性细胞死亡在肿瘤发生发展中的作为成为研究热点,所以对程序性细胞死亡机制的研究至关重要,本文将对各类型程序性细胞死亡的机制做简要综述。  相似文献   

3.
程序性细胞死亡是一种程序化的主动性细胞死亡,半胱胺酸天冬氨酸特异性蛋白酶家族(在该过程中起着不可忽视的作用.基于Caspase在程序性细胞死亡过程中所起的作用,将程序性细胞死亡分为两大类:Caspase依赖型和Caspase非依赖型.前者即典型的凋亡,后者包括自体吞噬、副凋亡、有丝分裂灾变、凋亡样程序性死亡、坏死样程序性死亡等.这些Caspase非依赖型的细胞程序性死亡途径与生理及病理现象密切相关.  相似文献   

4.
贺新强  吴鸿 《植物学报》2013,48(4):357-370
细胞程序死亡是多细胞生物体在内源发育信号或外源环境信号作用下在特定时间和空间发生的细胞死亡过程, 在植物的生长发育过程中起着重要作用。该文介绍了植物细胞程序死亡类型的几种划分方法、植物发育性细胞程序死亡研究常用的实验体系, 并着重概述有关植物发育性细胞程序死亡发生机制的研究进展。  相似文献   

5.
自噬是绝大部分真核细胞中一种依赖于溶酶体的极度保守的生理过程,是细胞内物质再循环的有效机制。适度的自噬是细胞抵御不良环境的生存方式,但当发生过度的自噬时,将引起细胞的死亡,这种死亡方式称为自噬性细胞死亡。自噬性细胞死亡不同于凋亡,表现为细胞中出现大量包裹着细胞质和细胞器的自噬体。越来越多的研究提示,自噬与自噬性细胞死亡与某些恶性肿瘤的发生、发展关系密切。在各种不利环境下,自噬可作为一种应急机制维持肿瘤细胞的生存,而自噬性细胞死亡诱发后又可清除肿瘤细胞。现就自噬与肿瘤的研究进展作一综述。  相似文献   

6.
GeneRegulationofProgrammedCellDeathYangJianminLiuLianrui(InstituteofGenetics,AcademiaSinica,Beijing100101)细胞死亡与细胞生长、分化和增殖一样是维持生物体平衡的重要环节。它是生命过程一个重要组成部分,只在近年来才引起生物学家和医学家的重视.细胞死亡现象称为Apoptosis,或称Programmedcelldeath(细胞程序化死亡),也有称为Suicide(细胞自杀现象)。细胞死亡(apoptosis)是在细胞内和细胞外因子的严格控制下~种有步骤有活性的生理性自行消亡过程,正在死亡的细胞形态上发生明显的变化,如胞浆浓缩,原生质膜形…  相似文献   

7.
NuMA(nuclear mitotic apparatus)是一个高分子量的细胞核有丝分裂器蛋白。自1980年发现至今已有30多年的历史。研究发现,NuMA对细胞有丝分裂过程中纺锤体的形成和结构维持、细胞分裂后期核重组均发挥重要作用。NuMA的过表达与恶性肿瘤发生发展相关,NuMA的降解将导致细胞分裂异常及细胞核骨架的分解。该文将对NuMA的表达及定位、可变剪接体、相互作用蛋白质及其在有丝分裂、不对称分裂及核移植胚胎早期发育等过程中的功能进行了系统综述。  相似文献   

8.
卵泡颗粒细胞凋亡和自噬在动物卵巢卵泡闭锁过程中发挥重要的调控作用。新近研究表明,铁死亡和焦亡也参与卵巢卵泡闭锁过程。铁死亡是一种铁依赖性脂质过氧化和活性氧(reactive oxygen species, ROS)积累引起的细胞死亡形式。研究证实,自噬和凋亡介导的卵泡闭锁过程中也有典型的铁死亡特征。细胞焦亡是依赖于Gasdermin蛋白的促炎性细胞死亡,可通过调节卵泡颗粒细胞调控卵巢繁殖性能。本文综述了几种细胞程序性死亡独立或相互作用参与调控卵泡闭锁的作用及机制,以期扩展卵泡闭锁机制的理论研究,为细胞程序性细胞死亡诱导卵泡闭锁的作用机制提供理论参考。  相似文献   

9.
程序性细胞死亡(PCD)是有别于病理性细胞死亡——坏死(necrosis)的一种生理性细胞死亡。目前已知,PCD在多细胞生物的发展和成年机体的代谢中均有重要作用。PCD在生物界普遍存在。近年发现PCD异常与某些疾病密切相关。PCD异常主要表现为PCD抑制和PCD过度两方面。PCD的发生由细胞的基因所控制,但是很多细胞外因素均可诱发PCD。弄清PCD在疾病发病中的作用有助于阐明疾病发病机制和探索新型疗法。1PCD与肿瘤PCD受抑制可诱发肿瘤,而通过一定方式诱发癌细胞的PCD又可有助于癌症治疗。肿瘤的发生是细胞内DNAbe变累积的结果…  相似文献   

10.
有丝分裂细胞死亡   总被引:6,自引:0,他引:6  
细胞死亡有坏死、凋亡、裂亡、自体吞噬等多种方式。细胞裂亡指细胞经过一次有丝分裂后才开始死亡的现象。本文综述了对于细胞裂亡这种新型细胞死亡方式的初步认识。  相似文献   

11.
Mitotic catastrophe is a poorly defined type of cell death linked to the abnormal activation of cyclin B/Cdk1. Here we propose that a conflict in cell cycle progression or DNA damage can lead to mitotic catastrophe, provided that cell cycle checkpoints are inhibited, in particular the DNA structure checkpoints and the spindle assembly checkpoint. Two subtypes of mitotic catastrophe can be distinguished. First, mitotic catastrophe can kill the cell during or close to the metaphase, in a p53-independent fashion, as this occurs in Chk2-inhibited heterokarya generated by fusion. Second, mitotic catastrophe can occur after failed mitosis, during the activation of the polyploidy checkpoint, in a partially p53-dependent fashion. In these conditions, cells die as a result of caspase activation and mitochondrial membrane permeabilization that constitute hallmarks of apoptosis. Prevention of caspase activation and/or mitochondrial damage avoids mitotic catastrophe, indicating that this form of cell death indeed constitutes a special case of apoptosis. Importantly, the suppression of mitotic catastrophe can favor asymmetric division and the generation of aneuploid cells. This delineates a molecular pathway through which failure to arrest the cell cycle and inhibition of apoptosis can favor the occurrence of cytogenetic abnormalities which are likely to participate in oncogenesis.  相似文献   

12.
Mitotic catastrophe is distinct from other cell death modes due to unique nuclear alterations characterized as multi and/or micronucleation. Mitotic catastrophe is a common and virtually unavoidable consequence during cancer therapy. However, a comprehensive understanding of mitotic catastrophe remains lacking. Herein, we summarize the anticancer drugs that induce mitotic catastrophe, including microtubule-targeting agents, spindle assembly checkpoint kinase inhibitors, DNA damage agents and DNA damage response inhibitors. Based on the relationships between mitotic catastrophe and other cell death modes, we thoroughly evaluated the roles played by mitotic catastrophe in cancer treatment as well as its advantages and disadvantages. Some strategies for overcoming its shortcomings while fully utilizing its advantages are summarized and proposed in this review. We also review how mitotic catastrophe regulates cancer immunotherapy. These summarized findings suggest that the induction of mitotic catastrophe can serve as a promising new therapeutic approach for overcoming apoptosis resistance and strengthening cancer immunotherapy.  相似文献   

13.
Mitotic catastrophe is an oncosuppressive mechanism that senses mitotic failure leading to cell death or senescence. As such, it protects against aneuploidy and genetic instability, and its induction in cancer cells by exogenous agents is currently seen as a promising therapeutic end point. Apoptin, a small protein from Chicken Anemia Virus (CAV), is known for its ability to selectively induce cell death in human tumor cells. Here, we show that apoptin triggers p53-independent abnormal spindle formation in osteosarcoma cells. Approximately 50% of apoptin-positive cells displayed non-bipolar spindles, a 10-fold increase as compared to control cells. Besides, tumor cells expressing apoptin are greatly limited in their progress through anaphase and telophase, and a significant drop in mitotic cells past the meta-to-anaphase transition is observed. Time-lapse microscopy showed that mitotic osteosarcoma cells expressing apoptin displayed aberrant mitotic figures and/or had a prolonged cycling time during mitosis. Importantly, all dividing cells expressing apoptin eventually underwent cell death either during mitosis or during the following interphase. We infer that apoptin can efficiently trigger cell death in dividing human tumor cells through induction of mitotic catastrophe. However, the killing activity of apoptin is not only confined to dividing cells, as the CAV-derived protein is also able to trigger caspase-3 activation and apoptosis in non-mitotic cancer cells.  相似文献   

14.
Activation of p53 by cellular stress may lead to either cell cycle arrest or apoptotic cell death. Restrictions in a cell's ability to halt the cell cycle might, in turn, cause mitotic catastrophe, a delayed type of cell death with distinct morphological features. Here, we have investigated the contribution of p53 and caspase-2 to apoptotic cell death and mitotic catastrophe in cisplatin-treated ovarian carcinoma cell lines. We report that both functional p53 and caspase-2 were required for the apoptotic response, which was preceded by translocation of nuclear caspase-2 to the cytoplasm. In the absence of functional p53, cisplatin treatment resulted in caspase-2-independent mitotic catastrophe followed by necrosis. In these cells, apoptotic functions could be restored by transient expression of wt p53. Hence, p53 appeared to act as a switch between apoptosis and mitotic catastrophe followed by necrosis-like lysis in this experimental model. Further, we show that inhibition of Chk2, and/or 14-3-3sigma deficiency, sensitized cells to undergo mitotic catastrophe upon treatment with DNA-damaging agents. However, apoptotic cell death seemed to be the final outcome of this process. Thus, we hypothesize that the final mode of cell death triggered by DNA damage in ovarian carcinoma cells is determined by the profile of proteins involved in the regulation of the cell cycle, such as p53- and Chk2-related proteins.  相似文献   

15.
Fragkos M  Beard P 《PloS one》2011,6(8):e22946
Cell death occurring during mitosis, or mitotic catastrophe, often takes place in conjunction with apoptosis, but the conditions in which mitotic catastrophe may exhibit features of programmed cell death are still unclear. In the work presented here, we studied mitotic cell death by making use of a UV-inactivated parvovirus (adeno-associated virus; AAV) that has been shown to induce a DNA damage response and subsequent death of p53-defective cells in mitosis, without affecting the integrity of the host genome. Osteosarcoma cells (U2OSp53DD) that are deficient in p53 and lack the G1 cell cycle checkpoint respond to AAV infection through a transient G2 arrest. We found that the infected U2OSp53DD cells died through mitotic catastrophe with no signs of chromosome condensation or DNA fragmentation. Moreover, cell death was independent of caspases, apoptosis-inducing factor (AIF), autophagy and necroptosis. These findings were confirmed by time-lapse microscopy of cellular morphology following AAV infection. The assays used readily revealed apoptosis in other cell types when it was indeed occurring. Taken together the results indicate that in the absence of the G1 checkpoint, mitotic catastrophe occurs in these p53-null cells predominantly as a result of mechanical disruption induced by centrosome overduplication, and not as a consequence of a suicide signal.  相似文献   

16.
Programmed cell death, or apoptosis, is a highly regulated process used to eliminate unwanted or damaged cells from multicellular organisms. The morphology of cells undergoing apoptosis is similar to cells undergoing both normal mitosis and an aberrant form of mitosis called mitotic catastrophe. During each of these processes, cells release substrate attachments, lose cell volume, condense their chromatin, and disassemble the nuclear lamina. The morphological similarities among cells undergoing these processes suggest that the underlying biochemical changes also may be related. The susceptibility of cells to apoptosis frequently depends on the differentiation state of the cell. Additionally, cell cycle checkpoints appear to link the cell cycle to apoptosis. Deregulation of the cell cycle components has been shown to induce mitotic catastrophe and also may be involved in triggering apoptosis. Some apoptotic cells express abnormal levels of cell cycle proteins and often contain active Cdc2, the primary kinase active during mitosis. Although cell cycle components may not be involved in all forms of apoptosis, in many instances cell proliferation and cell death may share common pathways.  相似文献   

17.
In Huh-7 hepatoma cells, low dose (LD) doxorubicin treatment induces cell death through mitotic catastrophe accompanying the formation of large cells with multiple micronuclei, whereas high dose (HD) doxorubicin induces apoptosis. In this study, we investigated the role of Cdc2 and Cdk2 kinase in the regulation of the two modes of cell death induced by doxorubicin. During HD doxorubicin-induced apoptosis, the histone H1-associated activities of Cdc2 and Cdk2 both progressively declined in parallel with reductions in cyclin A and cyclin B protein levels. In contrast, during LD doxorubicin-induced cell death through mitotic catastrophe, the Cdc2 and Cdk2 kinases were transiently activated 1 day post-treatment, with similar changes seen in the protein levels of cyclin A, cyclin B, and Cdc2. Treatment with roscovitine, a specific inhibitor of Cdc2 and Cdk2, significantly blocked LD doxorubicin-induced mitotic catastrophe and cell death, but did not affect HD doxorubicin-induced apoptosis in Huh-7, SNU-398, and SNU-449 hepatoma cell lines. Our results demonstrate that differential regulation of Cdc2 and Cdk2 activity by different doses of doxorubicin may contribute to the induction of two distinct modes of cell death in hepatoma cells, either apoptosis or cell death through mitotic catastrophe.  相似文献   

18.
The Bcr-Abl oncoprotein plays a major role in the development and progression of chronic myeloid leukemia and is a determinant of chemotherapy resistance occurring during the blast crisis phase of the disease. The aim of this article was to investigate the possibility of combating the resistance to apoptosis caused by Bcr-Abl by inducing an alternative cell death process. As a model of chronic myeloid leukemia, we employed Bcr-Abl-transfected mouse progenitor 32D cells with low and high Bcr-Abl expression levels corresponding to drug-sensitive and drug-resistant cells, respectively. The drug curcumin (diferuloylmethane), a known potent inducer of cell death in many cancer cells, was investigated for efficacy with Bcr-Abl-expressing cells. Curcumin strongly inhibited cell proliferation and affected cell viability by inducing apoptotic symptoms in all tested cells; however, apoptosis was a relatively late event. G(2)-M cell cycle arrest, together with increased mitotic index and cellular and nuclear morphology resembling those described for mitotic catastrophe, was observed and preceded caspase-3 activation and DNA fragmentation. Mitosis-arrested cells displayed abnormal chromatin organization, multipolar chromosome segregation, aberrant cytokinesis, and multinucleated cells-morphologic changes typical of mitotic catastrophe. We found that the mitotic cell death symptoms correlated with attenuated expression of survivin, a member of the chromosomal passenger complex, and mislocalization of Aurora B, the partner of survivin in the chromosomal passenger complex. Inhibition of survivin expression with small interfering RNA exhibited similar mitotic disturbances, thus implicating survivin as a major, albeit not the only, target for curcumin action. This study shows that curcumin can overcome the broad resistance to cell death caused by expression of Bcr-Abl and suggests that curcumin may be a promising agent for new combination regimens for drug-resistant chronic myeloid leukemia.  相似文献   

19.
Imidazoacridinone C-1311 is a DNA-targeting antitumor intercalator/alkylator currently undergoing Phase II clinical trials. Here, we elucidated the sequence of death responses to C-1311 in human leukemia MOLT4 cells using drug concentration (30 nM) that causes near complete cell growth inhibition at 48 h. Early (6-12 h) responses included transient accumulation of cells at the G2/M border followed by also transient rise in several mitotic markers. Mitotic attempts were largely abnormal, resulting in numerous multinucleated cells (peaking at 24-39 h and declining markedly at later times). These events, indicative of mitotic catastrophe, were not associated with immediate cell death. The fraction of necrotic cells did not exceed 3%. Also, the classical manifestations of apoptosis were marginal at 24 h and their progression clearly followed the decline in the fraction of mitotic and multinucleated cells. Quantification of several apoptotic markers (including phosphatidylserine externalization, apoptotic DNA breaks, mitochondrial dysfunction, caspase activation, and cell membrane integrity) showed a considerable progression and the shift from early to late apoptosis at later times. At 72 h, >80% of cells were apoptotic. Collectively, these findings show that C-1311-induced mitotic catastrophe is not the ultimate death event but rather a step precipitating delayed, albeit massive, apoptotic responses.  相似文献   

20.
Exposure of MDA-MB-231 and MCF-7/VP human breast carcinoma cells to theanthracyclines doxorubicin and WP631 induced polyploidy, formation of multinucleated cellsand cell death by mitotic catastrophe through caspase-dependent and caspase-independentmechanisms. In both cell lines, the antiproliferative effect of WP631 was higher than that ofdoxorubicin and a transient halt in G2/M was observed without cell senescence, while p53-dependent apoptosis did not occur in these cells. Mitotic catastrophe was linked to necrosis, butalso to apoptosis-like death, estimated by differential cell staining with Annexin-V-fluoresceinand propidium iodide. Drug-induced changes in the expression of c-myc and p21WAF1, and in theirrespective protein levels, were observed. They depended on the cell line, the anthracycline usedand its concentration, and they were consistent with the cell cycle progression through G2 tomitosis. Significant activation of caspase-2 and caspase-3 was only observed in MDA-MB-231cells treated with doxorubicin but not with WP631, indicating that caspases may be notmandatory for the occurrence of cell death through mitotic catastrophe. In MCF-7/VP cells,which do not express functional caspase-3, mitotic catastrophe was also induced.  相似文献   

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