共查询到20条相似文献，搜索用时 468 毫秒
1.
Deng X Yin X Allan R Lu DD Maurer CW Haimovitz-Friedman A Fuks Z Shaham S Kolesnick R 《Science (New York, N.Y.)》2008,322(5898):110-115
Ceramide engagement in apoptotic pathways has been a topic of controversy. To address this controversy, we tested loss-of-function (lf) mutants of conserved genes of sphingolipid metabolism in Caenorhabditis elegans. Although somatic (developmental) apoptosis was unaffected, ionizing radiation-induced apoptosis of germ cells was obliterated upon inactivation of ceramide synthase and restored upon microinjection of long-chain natural ceramide. Radiation-induced increase in the concentration of ceramide localized to mitochondria and was required for BH3-domain protein EGL-1-mediated displacement of CED-4 (an APAF-1-like protein) from the CED-9 (a Bcl-2 family member)/CED-4 complex, an obligate step in activation of the CED-3 caspase. These studies define CEP-1 (the worm homolog of the tumor suppressor p53)-mediated accumulation of EGL-1 and ceramide synthase-mediated generation of ceramide through parallel pathways that integrate at mitochondrial membranes to regulate stress-induced apoptosis. 相似文献
2.
[目的]以Marc-145细胞为模型,研究了伏马菌素B1能否导致细胞产生其他类型程序性细胞死亡。[方法]利用caspase抑制剂、蛋白合成抑制剂、非凋亡程序性细胞死亡necroptosis抑制剂及ROS抑制剂,分别抑制caspase活性、蛋白质合成、necroptosis和ROS,采用结晶紫染色和AnnexinV-FITC/PI双染分析这些抑制剂对伏马菌素B1诱导Marc-145细胞死亡的影响。[结果]caspase、necroptosis抑制剂和2种自由基抑制剂不能抑制伏马菌素B1诱导的Marc-145细胞死亡,但蛋白合成抑制剂则可以显著抑制伏马菌素B1诱导的Marc-145细胞死亡。[结论]伏马菌素B1所诱导的Marc-145细胞的死亡是一种受基因表达调控的程序性细胞死亡,但与caspase、ROS和nec-roptosis无关。 相似文献
3.
Yu SW Wang H Poitras MF Coombs C Bowers WJ Federoff HJ Poirier GG Dawson TM Dawson VL 《Science (New York, N.Y.)》2002,297(5579):259-263
Poly(ADP-ribose) polymerase-1 (PARP-1) protects the genome by functioning in the DNA damage surveillance network. PARP-1 is also a mediator of cell death after ischemia-reperfusion injury, glutamate excitotoxicity, and various inflammatory processes. We show that PARP-1 activation is required for translocation of apoptosis-inducing factor (AIF) from the mitochondria to the nucleus and that AIF is necessary for PARP-1-dependent cell death. N-methyl-N'-nitro-N-nitrosoguanidine, H2O2, and N-methyl-d-aspartate induce AIF translocation and cell death, which is prevented by PARP inhibitors or genetic knockout of PARP-1, but is caspase independent. Microinjection of an antibody to AIF protects against PARP-1-dependent cytotoxicity. These data support a model in which PARP-1 activation signals AIF release from mitochondria, resulting in a caspase-independent pathway of programmed cell death. 相似文献
4.
Wang X Wu YC Fadok VA Lee MC Gengyo-Ando K Cheng LC Ledwich D Hsu PK Chen JY Chou BK Henson P Mitani S Xue D 《Science (New York, N.Y.)》2003,302(5650):1563-1566
During apoptosis, phosphatidylserine, which is normally restricted to the inner leaflet of the plasma membrane, is exposed on the surface of apoptotic cells and has been suggested to act as an "eat-me" signal to trigger phagocytosis. It is unclear how phagocytes recognize phosphatidylserine. Recently, a putative phosphatidylserine receptor (PSR) was identified and proposed to mediate recognition of phosphatidylserine and phagocytosis. We report that psr-1, the Caenorhabditis elegans homolog of PSR, is important for cell corpse engulfment. In vitro PSR-1 binds preferentially phosphatidylserine or cells with exposed phosphatidylserine. In C. elegans, PSR-1 acts in the same cell corpse engulfment pathway mediated by intracellular signaling molecules CED-2 (homologous to the human CrkII protein), CED-5 (DOCK180), CED-10 (Rac GTPase), and CED-12 (ELMO), possibly through direct interaction with CED-5 and CED-12. Our findings suggest that PSR-1 is likely an upstream receptor for the signaling pathway containing CED-2, CED-5, CED-10, and CED-12 proteins and plays an important role in recognizing phosphatidylserine during phagocytosis. 相似文献
5.
【目的】TET（ten-eleven translocation）家族蛋白在调控胚胎和胎盘发育等过程中具有重要作用,输卵管与子宫内膜细胞的死亡平衡会影响受精卵及早期胚胎的发育。因此探讨TETs、细胞程序性死亡相关基因和附植相关基因在妊娠早期山羊输卵管及子宫角中的表达规律及其潜在调控作用,以期为研究胚胎发育及附植的分子机制奠定基础。【方法】以合川白山羊为研究对象,采集妊娠19d（P19）山羊子宫角及输卵管组织,以空配19d（C19）为对照,利用H.E染色观察C19组和P19组山羊子宫角组织形态,利用qRT-PCR技术检测了胚胎附植相关基因（WNT5a、OPN、VEGFA）、TETs（TET1、TET2、TET3）、细胞程序性死亡相关基因（凋亡相关基因（BAX、BCL2、Caspase9）、焦亡相关基因（GSDMD、NLRP3、Caspase1）和炎症相关基因（NF-kB、TNF-α））的相对表达,并分析了TETs及细胞程序性死亡相关基因在输卵管和子宫角组织的表达相关性。【结果】H.E染色结果显示,在P19组中山羊子宫角的腺体增多,形态多变。qRT-PCR结果显示,OPN在P19组山羊子宫角中的表达量极显著高于C19组（P＜0.01）,BAX/BCL2的表达量显著增加（P＜0.05）,而WNT5a和 VEGFA表达差异不显著;TET1、TET2、TET3在山羊子宫角及输卵管中均有表达,在C19组和P19组山羊子宫角中TET1及TET2的表达量极显著高于C19组和P19组中TET3的表达（P＜0.01）;在P19组山羊输卵管中TET2（P＜0.01）、NF-kB（P＜0.01）、Caspase1（P＜0.01）、GSDMD（P＜0.05）显著增高。相关性分析表明,输卵管中TET2与TET3（P＜0.01）、NF-kB（P＜0.01）、Caspase9（P＜0.05）显著正相关;子宫角中,TET3与VEGFA（P＜0.05）、WNT5a（P＜0.01）显著负相关,胚胎附植关键基因OPN与Caspase1（P＜0.01）、NLRP3（P＜0.05）、GSDMD（P＜0.05）显著正相关,而细胞焦亡关键基因GSDMD在输卵管与子宫角中均与Bax（P＜0.05）、Caspase1（P＜0.01）、NLRP3（P＜0.05）呈显著正相关。【结论】在妊娠早期山羊子宫角和输卵管中TETs表达与细胞程序性死亡部分基因表达具有一定的相关性,推测TETs与细胞凋亡或焦亡的发生对输卵管、受精卵、早期胚胎及子宫的发育具有一定的调控作用。胚胎附植关键基因OPN与焦亡相关基因显著相关,暗示妊娠早期子宫角中细胞焦亡的发生可能参与胚胎附植。为研究TETs通过细胞程序性死亡相关基因在妊娠早期输卵管及子宫角中的表达规律提供了理论参考。 相似文献
6.
Yu L Alva A Su H Dutt P Freundt E Welsh S Baehrecke EH Lenardo MJ 《Science (New York, N.Y.)》2004,304(5676):1500-1502
Caspases play a central role in apoptosis, a well-studied pathway of programmed cell death. Other programs of death potentially involving necrosis and autophagy may exist, but their relation to apoptosis and mechanisms of regulation remains unclear. We define a new molecular pathway in which activation of the receptor-interacting protein (a serine-threonine kinase) and Jun amino-terminal kinase induced cell death with the morphology of autophagy. Autophagic death required the genes ATG7 and beclin 1 and was induced by caspase-8 inhibition. Clinical therapies involving caspase inhibitors may arrest apoptosis but also have the unanticipated effect of promoting autophagic cell death. 相似文献
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8.
新城疫F48E9病毒体外诱导的鸡T淋巴细胞程序性死亡 总被引：6，自引：1，他引：5
应用流式细胞仪及DNA琼脂糖凝胶电泳技术研究了我国鸡新城疫标准强毒F48E9株体外诱导鸡T淋巴细胞的程序性死亡现象。同时,对其灭活毒以及从该毒株提取的囊膜蛋白诱导鸡T淋巴细胞的程序性死亡现象进行了观察,并以健康SPF鸡胚尿囊液作为对照。结果发现,F48E9株及其灭活毒体外均可诱导鸡T淋巴细胞发生程序性死亡,而从病毒中提取的囊膜蛋白及SPF鸡胚尿囊液无此特性。新城疫F48E9株体外诱导鸡T淋巴细胞程序性死亡这一现象初步表明,新城疫强毒F48E9株感染鸡T淋巴细胞数量的减少和功能的降低以及由此所致的感染鸡免疫功能的降低可能和病毒诱导鸡T淋巴细胞发生程序性死亡有关。 相似文献
9.
[目的]超低温保存后花粉生活力呈多种变化情况,已有研究表明活性氧(ROS)是超低温保存后花粉生活力变化的主要原因之一.因此,本研究探讨液氮冻存后花粉生活力与ROS诱导的氧化应激和细胞程序性死亡间的关系,以进一步揭示ROS在超低温保存后花粉生活力变化中的作用机制.[方法]以芍药'粉玉奴'的花粉为材料,对比分析超低温保存不... 相似文献
10.
Monoclonal antibody-mediated tumor regression by induction of apoptosis 总被引：166，自引：0，他引：166
B C Trauth C Klas A M Peters S Matzku P M?ller W Falk K M Debatin P H Krammer 《Science (New York, N.Y.)》1989,245(4915):301-305
To characterize cell surface molecules involved in control of growth of malignant lymphocytes, monoclonal antibodies were raised against the human B lymphoblast cell line SKW6.4. One monoclonal antibody, anti-APO-1, reacted with a 52-kilodalton antigen (APO-1) on a set of activated human lymphocytes, on malignant human lymphocyte lines, and on some patient-derived leukemic cells. Nanogram quantities of anti-APO-1 completely blocked proliferation of cells bearing APO-1 in vitro in a manner characteristic of a process called programmed cell death or apoptosis. Cell death was preceded by changes in cell morphology and fragmentation of DNA. This process was distinct from antibody- and complement-dependent cell lysis and was mediated by the antibody alone. A single intravenous injection of anti-APO-1 into nu/nu mice carrying a xenotransplant of a human B cell tumor induced regression of this tumor within a few days. Histological thin sections of the regressing tumor showed that anti-APO-1 was able to induce apoptosis in vivo. Thus, induction of apoptosis as a consequence of a signal mediated through cell surface molecules like APO-1 may be a useful therapeutic approach in treatment of malignancy. 相似文献
11.
超敏反应(HR)是植物抗性反应激活所表现出的最为常见的特征。植物的超敏性细胞死亡在生物化学和形态学上有许多特征与动物的细胞凋亡相似,并且受寄主植物的 R基因和病原菌的avr 基因产物相互作用所控制,R基因产物与参与动物细胞凋亡的CED-4和APAF-1 蛋白有相似之处,因此,超敏性细胞死亡明显是细胞程序化死亡(PCD)的一种形式。HR中有多种信号分子的参与,活性氧是诱导 HR的一个重要因子,并且活性氧的产生与水杨酸(SA)有着直接的关系。HR很可能是作为一个信号系统而不是直接作为植物的一种防御机制。 相似文献
12.
【目的】检验Steedman’swax包埋切片DAPI染色法是否适用于观察花生根尖细胞核形态。【方法】分别采取100μmol/L AlCl3处理不同时间（0、4、8、12 h）后两个花生品种（铝敏感型中花2号和耐铝型99-1507）的根尖,经过Steedman’s wax包埋切片等一系列过程,利用荧光染料DAPI染色观察细胞核形态变化。【结果】100μmol/L AlCl3可引起花生根尖细胞核形态发生改变,核质浓缩、核边缘化、呈新月状等,具有明显的PCD特征。花生根尖细胞在铝胁迫下发生PCD,PCD程度与花生耐铝性呈负相关,与处理时间呈正相关。【结论】Steedman’swax包埋切片DAPI染色法是一种快速、高效的适用于观察花生根尖细胞核形态的方法。 相似文献
13.
Prevention of apoptosis by a baculovirus gene during infection of insect cells 总被引：106，自引：0，他引：106
Programmed cell death is an active process of self destruction that is important in both the development and maintenance of multicellular animals. The molecular mechanisms controlling activation or suppression of programmed cell death are largely unknown. Apoptosis, a morphologically and biochemically defined type of programmed cell death commonly seen in vertebrates, was found to be initiated during baculovirus replication in insect cells. A specific viral gene product, p35, was identified as being responsible for blocking the apoptotic response. Identification of the function of this gene will allow further definition of the molecular pathways involved in the regulation of programmed cell death and may identify the role of apoptosis in invertebrate viral defense systems. 相似文献
14.
HarpinXoo是水稻白叶枯病菌分泌的蛋白质，用harpinXoo注射烟草后20 h，可表现过敏性细胞死亡（hypersensitive cell death, HCD）。对harpinXoo诱导的烟草叶片用DNA特异染料（DAPI）染色后经荧光显微镜观察发现，烟草细胞在harpinXoo诱导后不同时间表现明显的染色质浓缩；对诱导后的烟草DNA经2％琼脂糖凝胶电泳发现，诱导后12 h烟草DNA开始出现弥散的条带，24 h后弥散的小片段大量增加；定量RT-PCR检测发现，harpinXoo诱导的烟草HCD早期即有标志基因hin1和hsr203J的诱导表达。这些结果表明，harpinXoo诱导的烟草细胞死亡，是植物的一种主动反应，具有细胞编程死亡的重要特征。 相似文献
15.
Dorrello NV Peschiaroli A Guardavaccaro D Colburn NH Sherman NE Pagano M 《Science (New York, N.Y.)》2006,314(5798):467-471
The tumor suppressor programmed cell death protein 4 (PDCD4) inhibits the translation initiation factor eIF4A, an RNA helicase that catalyzes the unwinding of secondary structure at the 5' untranslated region (5'UTR) of messenger RNAs (mRNAs). In response to mitogens, PDCD4 was rapidly phosphorylated on Ser67 by the protein kinase S6K1 and subsequently degraded via the ubiquitin ligase SCF(betaTRCP). Expression in cultured cells of a stable PDCD4 mutant that is unable to bind betaTRCP inhibited translation of an mRNA with a structured 5'UTR, resulted in smaller cell size, and slowed down cell cycle progression. We propose that regulated degradation of PDCD4 in response to mitogens allows efficient protein synthesis and consequently cell growth. 相似文献
16.
【目的】对拟南芥肌醇磷酸合酶AtIPS1进行亚细胞水平定位,并验证AtIPS1与细胞程序化死亡（PCD）相关蛋白ATXR5或ATXR6的相互作用。【方法】构建pAtIPS1::AtIPS1-GFP融合基因表达载体,并分别转化烟草BY-2细胞和拟南芥植株,共聚焦显微镜下观察绿色荧光蛋白GFP的分布。采用双分子荧光互补（BiFC）技术分析AtIPS1与ATXR5/6的相互作用,并观察突变体atips1的表型。【结果】AtIPS1定位于细胞质和细胞核。AtIPS1与ATXR5和ATXR6之间存在相互作用,且互作位点与AtIPS1的细胞定位一致。突变体atips1叶片上自然产生细胞死亡的表型,外源增加肌醇或AtIPS1超表达可恢复突变体的野生型表型,叶片不再出现坏死斑。【结论】AtIPS1突变可导致植物细胞死亡;AtIPS1定位于细胞质和细胞核;AtIPS1通过与ATXR5/6互作参与了植物PCD的调控。 相似文献
17.
[目的]从细胞核的形态变化观察干旱是否诱导苹果属植物发生细胞程序性死亡,并且鉴定DAPI是否是观察细胞形态学的较好方法。[方法]以抗旱能力较强的八棱海棠和抗旱性较弱的平邑甜茶幼苗为试验材料,用20%聚乙二醇模拟干旱,对这2种幼苗根系进行处理,并对处理的新根经DAPI染色在紫外光下照射。[结果]经DAPI染色在紫外光（UV）照射下,正常新根细胞核发出均匀的蓝色荧光,而经干旱处理后新根的细胞出现染色质凝集、细胞核缩小、变形、解体、形成凋亡小体等细胞凋亡的形态学特征。[结论]在干旱诱导苹果属植物死亡过程中,有一个阶段存在明显的细胞程序性死亡过程,且DAPI荧光染色是观察细胞程序性死亡的较好方法。 相似文献
18.
不结球白菜小孢子胚胎发生过程及发育途径研究 总被引：3，自引：0，他引：3
采用FDA荧光染色法对小孢子游离培养的发育过程进行了观察。结果表明:不结球白菜花粉母细胞减数分裂释放出的小孢子发育到单核靠边期及稍后时期染色最深、活力最强。多数游离小孢子培养经历的发育过程与合子胚相似,并且胚胎发育迅速,6～9 d产生大量球型胚,13 d开始出现子叶型胚胎。小孢子胚胎发育途径既有对称分裂并产生胚胎的途径(B途径),也有第1次不对称有丝分裂的方式;第1次不对称分裂后,既有营养细胞单独发育成胚的现象(A途径),也有营养细胞和生殖细胞共同发育成胚的现象(E途径),但未发现生殖细胞单独发育成胚的现象。 相似文献
19.
Darland-Ransom M Wang X Sun CL Mapes J Gengyo-Ando K Mitani S Xue D 《Science (New York, N.Y.)》2008,320(5875):528-531
The asymmetrical distribution of phospholipids on the plasma membrane is critical for maintaining cell integrity and physiology and for regulating intracellular signaling and important cellular events such as clearance of apoptotic cells. How phospholipid asymmetry is established and maintained is not fully understood. We report that the Caenorhabditis elegans P-type adenosine triphosphatase homolog, TAT-1, is critical for maintaining cell surface asymmetry of phosphatidylserine (PS). In animals deficient in tat-1, PS is abnormally exposed on the cell surface, and normally living cells are randomly lost through a mechanism dependent on PSR-1, a PS-recognizing phagocyte receptor, and CED-1, which contributes to recognition and engulfment of apoptotic cells. Thus, tat-1 appears to function in preventing appearance of PS in the outer leaflet of plasma membrane, and ectopic exposure of PS on the cell surface may result in removal of living cells by neighboring phagocytes. 相似文献
20.
Erythropoietin retards DNA breakdown and prevents programmed death in erythroid progenitor cells 总被引：62，自引：0，他引：62
The mechanism by which erythropoietin controls mammalian erythrocyte production is unknown. Labeling experiments in vitro with [3H]thymidine demonstrated DNA cleavage in erythroid progenitor cells that was accompanied by DNA repair and synthesis. Erythropoietin reduced DNA cleavage by a factor of 2.6. In the absence of erythropoietin, erythroid progenitor cells accumulated DNA cleavage fragments characteristic of those found in programmed cell death (apoptosis) by 2 to 4 hours and began dying by 16 hours. In the presence of erythropoietin, the progenitor cells survived and differentiated into reticulocytes. Thus, apoptosis is a major component of normal erythropoiesis, and erythropoietin controls erythrocyte production by retarding DNA breakdown and preventing apoptosis in erythroid progenitor cells. 相似文献