共查询到20条相似文献，搜索用时 31 毫秒
1.
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
2.
A current view is that cytotoxic stress, such as DNA damage, induces apoptosis by regulating the permeability of mitochondria. Mitochondria sequester several proteins that, if released, kill by activating caspases, the proteases that disassemble the cell. Cytokines activate caspases in a different way, by assembling receptor complexes that activate caspases directly; in this case, the subsequent mitochondrial permeabilization accelerates cell disassembly by amplifying caspase activity. We found that cytotoxic stress causes activation of caspase-2, and that this caspase is required for the permeabilization of mitochondria. Therefore, we argue that cytokine-induced and stress-induced apoptosis act through conceptually similar pathways in which mitochondria are amplifiers of caspase activity rather than initiators of caspase activation. 相似文献
3.
Distinctive roles of PHAP proteins and prothymosin-alpha in a death regulatory pathway 总被引：1，自引：0，他引：1
Jiang X Kim HE Shu H Zhao Y Zhang H Kofron J Donnelly J Burns D Ng SC Rosenberg S Wang X 《Science (New York, N.Y.)》2003,299(5604):223-226
A small molecule, alpha-(trichloromethyl)-4-pyridineethanol (PETCM), was identified by high-throughput screening as an activator of caspase-3 in extracts of a panel of cancer cells. PETCM was used in combination with biochemical fractionation to identify a pathway that regulates mitochondria-initiated caspase activation. This pathway consists of tumor suppressor putative HLA-DR-associated proteins (PHAP) and oncoprotein prothymosin-alpha (ProT). PHAP proteins promoted caspase-9 activation after apoptosome formation, whereas ProT negatively regulated caspase-9 activation by inhibiting apoptosome formation. PETCM relieved ProT inhibition and allowed apoptosome formation at a physiological concentration of deoxyadenosine triphosphate. Elimination of ProT expression by RNA interference sensitized cells to ultraviolet irradiation-induced apoptosis and negated the requirement of PETCM for caspase activation. Thus, this chemical-biological combinatory approach has revealed the regulatory roles of oncoprotein ProT and tumor suppressor PHAP in apoptosis. 相似文献
4.
5.
Wild-type nonneuronal cells extend survival of SOD1 mutant motor neurons in ALS mice 总被引：1，自引：0，他引：1
Clement AM Nguyen MD Roberts EA Garcia ML Boillée S Rule M McMahon AP Doucette W Siwek D Ferrante RJ Brown RH Julien JP Goldstein LS Cleveland DW 《Science (New York, N.Y.)》2003,302(5642):113-117
The most common inherited [correct] form of amyotrophic lateral sclerosis (ALS), a neurodegenerative disease affecting adult motor neurons, is caused by dominant mutations in the ubiquitously expressed Cu-Zn superoxide dismutase (SOD1). In chimeric mice that are mixtures of normal and SOD1 mutant-expressing cells, toxicity to motor neurons is shown to require damage from mutant SOD1 acting within nonneuronal cells. Normal motor neurons in SOD1 mutant chimeras develop aspects of ALS pathology. Most important, nonneuronal cells that do not express mutant SOD1 delay degeneration and significantly extend survival of mutant-expressing motor neurons. 相似文献
6.
Soengas MS Alarcón RM Yoshida H Giaccia AJ Hakem R Mak TW Lowe SW 《Science (New York, N.Y.)》1999,284(5411):156-159
The ability of p53 to promote apoptosis in response to mitogenic oncogenes appears to be critical for its tumor suppressor function. Caspase-9 and its cofactor Apaf-1 were found to be essential downstream components of p53 in Myc-induced apoptosis. Like p53 null cells, mouse embryo fibroblast cells deficient in Apaf-1 and caspase-9, and expressing c-Myc, were resistant to apoptotic stimuli that mimic conditions in developing tumors. Inactivation of Apaf-1 or caspase-9 substituted for p53 loss in promoting the oncogenic transformation of Myc-expressing cells. These results imply a role for Apaf-1 and caspase-9 in controlling tumor development. 相似文献
7.
Chen M Wang YH Wang Y Huang L Sandoval H Liu YJ Wang J 《Science (New York, N.Y.)》2006,311(5764):1160-1164
Apoptosis in the immune system is critical for maintaining self-tolerance and preventing autoimmunity. Nevertheless, inhibiting apoptosis in lymphocytes is not alone sufficient to break self-tolerance, suggesting the involvement of other cell types. We investigated whether apoptosis in dendritic cells (DCs) helps regulate self-tolerance by generating transgenic mice expressing the baculoviral caspase inhibitor, p35, in DCs (DC-p35). DC-p35 mice displayed defective DC apoptosis, resulting in their accumulation and, in turn, chronic lymphocyte activation and systemic autoimmune manifestations. The observation that a defect in DC apoptosis can independently lead to autoimmunity is consistent with a central role for these cells in maintaining immune self-tolerance. 相似文献
8.
【目的】小麦籽粒超氧化物歧化酶活性对小麦面粉色泽和营养品质具有重要影响,挖掘与小麦籽粒超氧化物歧化酶（superoxide dismutase,SOD）活性显著关联位点及候选基因,为揭示小麦籽粒SOD活性的遗传机理和小麦面粉色泽的遗传改良奠定基础。【方法】采用氮蓝四唑（nitro-blue tetrazolium,NBT）光化还原法对3个环境下种植的212份普通小麦品种（系）进行SOD活性检测,结合90K SNP芯片的16 705个高质量SNP标记对小麦籽粒SOD活性进行全基因组关联分析（genome-wide association study,GWAS）,并对稳定遗传的显著关联位点进行候选基因的挖掘。【结果】不同环境下,各小麦品种（系）间的SOD活性表现出丰富的表型变异,变异系数为4.34%—5.23%,相关系数介于0.60—0.90（P<0.001）。多态性信息含量（polymorphic information content,PIC）为0.24—0.29。全基因组连锁不平衡（linkage disequilibrium,LD）衰减距离为7 Mb。群体结构分析表明,供试材料可分为3个亚群。GWAS分析结果显示,共检测到29个与SOD活性显著关联位点（P≤0.001）,分布在1A、1B、2A、2B、2D、3B、3D、4B、4D、5A、5B、5D、6A、6B、6D和7B染色体上,单个位点可解释5.47%—32.43%的表型变异,其中14个位点在2个及以上环境下均被检测到。9个显著关联位点在3个环境下被同时检测到,分布于1B、2B、4B、5A、5B、6B和6D染色体,贡献率为6.21%—16.62%。对稳定遗传的显著关联位点进行候选基因的挖掘,共挖掘TraesCS2B01G567600、TraesCS3D01G069900、TraesCS3D01G070200、TraesCS5B01G525700、TraesCS5B01G373700、TraesCS6A01G021400和TraesCS6D01G431500等7个SOD基因和TraesCS5A01G263500、TraesCS6B01G707800等2个与SOD活性相关的候选基因,候选基因的功能主要与抑制细胞活性氧积累及参与抗氧化剂再生过程有关。【结论】检测到与小麦籽粒SOD活性显著关联的29个SNP位点,共筛选出7个SOD基因和2个与SOD活性有关的候选基因。 相似文献
9.
目的:探讨皮肤鳞状细胞癌(简称鳞癌)、基底细胞癌(简称基癌)组织中FADD、caspase-3(简称casp-3)的表达及其与细胞凋亡的关系。方法:应用原位末端标记(TUNEL)和SABC免疫组化技术检测48例鳞癌、41例基癌中FADD、casp-3表达及细胞凋亡。结果:鳞癌中FADD、casp-3表达及凋亡指数(A I)均明显高于基癌(P<0.01),两种表皮肿瘤的FADD、casp-3表达与A I均呈正相关(r=0.521,P<0.05),FADD与casp-3之间的表达亦呈正相关(r=0.437,P<0.05)。低分化鳞癌中的casp-3表达和A I低于高分化者(P<0.05),鳞癌原发灶中的A I高于转移灶(P<0.01)。结论:Fas凋亡途径可能是鳞癌、基癌的主要凋亡途径,FADD、casp-3是鳞癌、基癌细胞凋亡中重要的促凋亡因子,并有相互协同促凋亡作用。 相似文献
10.
水稻和稗草ALS活性测定及农美利选择性机理研究 总被引：9，自引：0，他引：9
乙酰乳酸合成酶（ＡＬＳ）是除草剂主要作用靶标,新型除草剂农美利（ｂｉｓｐｙｒｉｂａｃ－ｓｏｄｉｕｍ）即是通过抑制ＡＬＳ的活性使支链氨基酸的生物合成受阻而达到除草目的。作者利用ＡＬＳ脱羧产物３－羟基丁酮与肌酸及甲萘酚形成的复合物,采用比色法测定ＡＬＳ活性和农美利的抑制作用,以明确农美利对水稻和稗草的选择性机理。研究结果表明,水稻和稗草体内ＡＬＳ酶促反应复合产物的吸收峰为５２０ｎｍ;ＡＬＳ活性在不同水稻品种和不同杂划体内各不相同,不同水稻品种依次为汕优６３、秀水１１〉样湖８４〈嘉育２９３,不同杂草依次为稗草、鳢肠〉异型莎草〉千金子。体内法测定农美利对植物体内ＡＬＳ的抑制程度结果显示,水稻ＡＬＳ受抑制快于稗草,恢复也快;不同水稻品种ＡＬＳ以嘉育２９３受抑制较快,秀水１１抑制程度较大,而祥湖８４和汕优６３受抑制慢且程度 相似文献
11.
Srikanth CV Wall DM Maldonado-Contreras A Shi HN Zhou D Demma Z Mumy KL McCormick BA 《Science (New York, N.Y.)》2010,330(6002):390-393
The enteric pathogen Salmonella enterica serovar Typhimurium causes food poisoning resulting in gastroenteritis. The S. Typhimurium effector Salmonella invasion protein A (SipA) promotes gastroenteritis by functional motifs that trigger either mechanisms of inflammation or bacterial entry. During infection of intestinal epithelial cells, SipA was found to be responsible for the early activation of caspase-3, an enzyme that is required for SipA cleavage at a specific recognition motif that divided the protein into its two functional domains and activated SipA in a manner necessary for pathogenicity. Other caspase-3 cleavage sites identified in S. Typhimurium appeared to be restricted to secreted effector proteins, which indicates that this may be a general strategy used by this pathogen for processing of its secreted effectors. 相似文献
12.
Estévez AG Crow JP Sampson JB Reiter C Zhuang Y Richardson GJ Tarpey MM Barbeito L Beckman JS 《Science (New York, N.Y.)》1999,286(5449):2498-2500
Mutations in copper, zinc superoxide dismutase (SOD) have been implicated in the selective death of motor neurons in 2 percent of amyotrophic lateral sclerosis (ALS) patients. The loss of zinc from either wild-type or ALS-mutant SODs was sufficient to induce apoptosis in cultured motor neurons. Toxicity required that copper be bound to SOD and depended on endogenous production of nitric oxide. When replete with zinc, neither ALS-mutant nor wild-type copper, zinc SODs were toxic, and both protected motor neurons from trophic factor withdrawal. Thus, zinc-deficient SOD may participate in both sporadic and familial ALS by an oxidative mechanism involving nitric oxide. 相似文献
13.
Hatsugai N Kuroyanagi M Yamada K Meshi T Tsuda S Kondo M Nishimura M Hara-Nishimura I 《Science (New York, N.Y.)》2004,305(5685):855-858
Programmed cell death (PCD) in animals depends on caspase protease activity. Plants also exhibit PCD, for example as a response to pathogens, although a plant caspase remains elusive. Here we show that vacuolar processing enzyme (VPE) is a protease essential for a virus-induced hypersensitive response that involves PCD. VPE deficiency prevented virus-induced hypersensitive cell death in tobacco plants. VPE is structurally unrelated to caspases, although VPE has a caspase-1 activity. Thus, plants have evolved a regulated cellular suicide strategy that, unlike PCD of animals, is mediated by VPE and the cellular vacuole. 相似文献
14.
Cells undergoing apoptosis during development are removed by phagocytes, but the underlying mechanisms of this process are not fully understood. Phagocytes lacking the phosphatidylserine receptor (PSR) were defective in removing apoptotic cells. Consequently, in PSR-deficient mice, dead cells accumulated in the lung and brain, causing abnormal development and leading to neonatal lethality. A fraction of PSR knockout mice manifested a hyperplasic brain phenotype resembling that of mice deficient in the cell death-associated genes encoding Apaf-1, caspase-3, and caspase-9, which suggests that phagocytes may also be involved in promoting apoptosis. These data demonstrate a critical role for PSR in early stages of mammalian organogenesis and suggest that this receptor may be involved in respiratory distress syndromes and congenital brain malformations. 相似文献
15.
东莞大蕉超表达拟南芥CBF1基因及其抗寒性检测 总被引：2，自引：1，他引：1
【目的】研究超表达拟南芥CBF1基因（AtCBF1）对大蕉抗寒性的影响,为从大蕉克隆抗寒相关基因奠定基础。【方法】采用农杆菌介导法转化东莞大蕉的胚性细胞悬浮系,获得转AtCBF1基因的大蕉植株;利用GUS组织染色、PCR、RT-PCR以及RT-qPCR对转基因植株进行鉴定;比较低温处理后的转基因株系和对照的冷害特征以及超氧化物歧化酶（SOD）活性和丙二醛（MDA）含量等生理生化指标,鉴定转基因大蕉植株的抗寒能力。【结果】试验共获得6个抗性再生转化系。GUS组织染色结果表明,除T1外,其余均为阳性;PCR鉴定结果表明,AtCBF1在6个抗性再生转化系均为阳性,而GUS基因在T1转化系中没有检测出;RT-PCR结果表明,AtCBF1在6个转化系均得到表达,对T1、T2和T3 3个转化系进行RT-qPCR检测发现,AtCBF1基因在3个转基因株系表达水平存在差异;在低温处理下,转基因植株的叶片相对电导率、MDA的累积都低于非转基因植株,而SOD总活性高于对照;低温处理条件下,转基因植株叶片的冷害症状明显轻于对照。【结论】AtCBF1在大蕉中超表达,具有增强大蕉SOD活性,降低因低温导致的MDA含量和离子渗漏率,缓解质膜过氧程度,进而改善大蕉植株抗低温胁迫的能力。 相似文献
16.
Mannick JB Hausladen A Liu L Hess DT Zeng M Miao QX Kane LS Gow AJ Stamler JS 《Science (New York, N.Y.)》1999,284(5414):651-654
Only a few intracellular S-nitrosylated proteins have been identified, and it is unknown if protein S-nitrosylation/denitrosylation is a component of signal transduction cascades. Caspase-3 zymogens were found to be S-nitrosylated on their catalytic-site cysteine in unstimulated human cell lines and denitrosylated upon activation of the Fas apoptotic pathway. Decreased caspase-3 S-nitrosylation was associated with an increase in intracellular caspase activity. Fas therefore activates caspase-3 not only by inducing the cleavage of the caspase zymogen to its active subunits, but also by stimulating the denitrosylation of its active-site thiol. Protein S-nitrosylation/denitrosylation can thus serve as a regulatory process in signal transduction pathways. 相似文献
17.
Gurney ME 《Science (New York, N.Y.)》1995,269(5221):149
In the report "Motor neuron degeneration in mice that express a human Cu, Zn super-oxide dismutase mutation" by M. E. Gurney et al. (17 June 1994, p. 1772)(1), a systematic, 10-fold error was made in calculating the dilutions of brain extract used for determinations of total brain superoxide dismutase (SOD) activity shown in column 6 of table 1 (p. 1774). Each value reported should have been reduced by that factor, for example, the total SOD activity reported for the G1 line should have been 4.26 +/- 0.2 SOD (U)/total protein (microg), not 42.6 +/- 2.1 U/microg, and so forth. 相似文献
18.
异源表达Peu-miR473 a增强拟南芥的抗旱性 总被引：1，自引：1，他引：0
为了探究胡杨miR473a基因的功能,本文克隆了miR473a的前体Pre-Peu-miR473a,并利用农杆菌花序侵染法将其遗传转化入拟南芥。通过普通PCR和β-葡萄糖苷酸酶(GUS)组织化学染色检测获得CaMV35S: miR473a过表达植株,然后对转基因和野生型植株在甘露醇模拟高渗环境与土壤自然干旱条件下的生长状况及各项生理指标进行评价。结果表明,胡杨miR473a前体长度为100 bp,与毛果杨前体序列相似度为100%,可以形成完美的二级茎环结构。相比于野生型,过表达胡杨miR473a的拟南芥在200 mmol/L甘露醇胁迫条件下的萌发率、根长和生长状况都优于野生型;在土壤干旱处理条件下,转基因拟南芥的株高、相对含水量、脯氨酸含量以及光系统Ⅱ(PSⅡ)最大光合效率均显著高于野生型10%以上(P0.05)。半定量PCR检测显示:Peu-miR473a参与胡杨受干旱胁迫的正调控,杨树中预测的靶基因Potri.012G093900、Potri.007G100200、Potri.009G165300、Potri.004G204400受干旱胁迫的负调控;拟南芥中预测的靶基因AT1G24530、AT5G45000、AT5G46070及AT3G52950在转基因株系中表达量下降。初步预测它们有可能被miR473a靶向调控。本研究表明,miR473a基因在干旱胁迫条件下通过调控植株的抗脱水能力和渗透调节能力发挥一定抗旱作用。 相似文献
19.
转Bar基因稻谷对小鼠肝功能若干参数的影响 总被引：1，自引：0，他引：1
通过对SPF级昆明小鼠喂食含量分别为20%、40%、60%转抗除草剂(Bar)基因稻谷,繁殖F1、F2代,并持续观察F1、F2代小鼠的日常行为、肝脏器官指数及血液生化指标,研究了转抗除草剂Bar基因稻谷对小鼠肝功能若干参数的影响。结果表明:用转Bar基因稻谷喂养并未对小鼠日常行为产生明显影响。F1、F2代供试小鼠各剂量的转基因组与常规对照组小鼠肝脏器官指数无明显差异(P>0.05)。F1代小鼠中A组和C组的白/球比、谷草转氨酶、谷丙转氨酶、碱性磷酸酶、乳酸脱氢酶等指标无显著性差异(P>0.05),B组的白/球比、谷草转氨酶、谷丙转氨酶、乳酸脱氢酶等指标无显著性差异(P>0.05),但碱性磷酸酶指标出现显著性差异(P<0.05);F2代小鼠中A、B、C组白/球比、谷草转氨酶、谷丙转氨酶、碱性磷酸酶、乳酸脱氢酶5项指标均无显著性差异(P>0.05)。F1、F2代A、B、C组的葡萄糖、甘油三酯和总胆固醇3项指标均无显著性差异(P>0.05)。在试验处理及时间内,与对照常规稻谷相比,用转基因稻谷喂养小鼠对其肝脏功能基本无影响。 相似文献
20.
A protective role of resveratrol against the effects of immobilization stress in corpora lutea of mice in early pregnancy 
下载免费PDF全文
下载免费PDF全文 Saif ULLAH Sheeraz MUSTAFA Wael ENNAB Muhammad JAN Muhammad SHAFIQ Ngekure M. X. KAVITA Lü Zeng-peng MAO Da-gan SHI Fang-xiong 《农业科学学报》2020,19(7):1857-1866
In the present study, we aimed to investigate a protective role for resveratrol against the effects of immobilization stress on corpora lutea(CL) of mice in early pregnancy. A total of 45 early-pregnant mice were divided into no immobilization stress(NIS) group, immobilization stress(IS) group, and immobilization and resveratrol treatment(IS+RES) group(n=15). Mice were immobilized in plastic tubes(50 mL) for 3 h per day during day 1 to 7 of pregnancy. In the IS+RES group, 5 mg kg–1 d–1 of resveratrol was administered just prior to application of stress. We analyzed apoptotic activity in CL by Western blotting analysis(WB), transmission electron microscopy(TEM), and immunohistochemistry(IHC). Serum progesterone levels were examined with radioimmunoassay(RIA). IHC results showed that the intensity of positive staining for Bax was increased, and for Bcl-2 was decreased in CL after IS, while resveratrol treatment reversed the positive staining for Bax and Bcl-2. WB revealed that immobilization stress up-regulated the expression of Bax and caspase-9, and downregulated Bcl-2 expression, while resveratrol treatment attenuated the effects of immobilization stress on the expression of Bax, Bcl-2 and caspase-9. According to our TEM results, apoptosis as defined by chromatin condensation was found in CL after immobilization stress, while resveratrol inhibited the apoptosis. We also demonstrated that immobilization stress decreased progesterone concentrations and ovarian expression of StAR, while resveratrol restored the concentrations of progesterone and expression of StAR back to normal. These results indicated that immobilization stress induced luteal regression while resveratrol inhibited luteal regression, suggesting that resveratrol plays a protective role on corpora lutea of mice during early pregnancy. 相似文献