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1.
大部分化疗药物可以促进活性氧(ROS)产生,同时ROS可以诱导细胞凋亡。本研究构建了一种有机砷化合物N-(4-(1,3,2-dithiarsinan-2-yl)phenyl)acrylamide(AAZ2),其可通过促进ROS产生诱导胃癌线粒体依赖的细胞凋亡。具体机制为AAZ2通过靶向丙酮酸脱氢酶激酶1(PDK1)导致葡萄糖代谢改变和氧化应激,继而抑制PI3K/AKT/m TOR通路,最终激活半胱天冬酶(caspase)依赖的细胞凋亡。此外,体内实验也证实了AAZ2可以抑制胃癌移植瘤的生长。综上,在胃癌中,AAZ2可以通过靶向PDK1影响葡萄糖代谢及随后的氧化应激反应,抑制PI3K/AKT/m TOR信号通路,最终诱发线粒体依赖的细胞凋亡。  相似文献   

2.
细胞凋亡是细胞与生俱来的一种机制 ,是最常见的细胞生理性死亡形式。高浓度的活性氧是启动细胞凋亡的信号 ,它是在电子传给末端氧化酶之前漏出呼吸链与氧反应生成的。活性氧水平的升高使线粒体上非特异性的通透性转运孔道开放 ,于是原来位于线粒体膜间隙的某些与凋亡有关的活性物质释放到细胞液中 ,激活胱天蛋白酶 ,引起细胞凋亡。位于凋亡后期的效应因子也可被不同的凋亡前期信使分子所激活 ,而IAP蛋白则能通过直接抑制胱天蛋白酶家族蛋白的活化过程而抑制凋亡的发生。  相似文献   

3.
细胞凋亡是细胞与生俱来的一种机制,是最常见的细胞生理性死亡形式。高浓度的活性氧是启动细胞凋亡的信号。它是在电子传给末端氧化酶之前漏出呼吸链与氧反应生成的。活性氧水平的升高使线粒体上非特异性的通透性转运孔道开放,于是原来位于线粒体膜间隙的某些与凋亡有关的活性物质释放到细胞液中,激活胱天蛋白酶,引起细胞凋亡。位于凋亡后期的效应因子也可被不同的凋亡前期信使分子所激活,而IAP蛋白则能通过直接抑制胱天蛋白酶家族蛋白的活化过程而抑制凋亡的发生。  相似文献   

4.
为探究异乌药内酯诱导细胞内活性氧的产生在介导线粒体凋亡途径中的作用及对肺癌A549细胞凋亡的影响,将A549细胞分为对照组(DMSO)、异乌药内酯处理组(15μmol/L)、抗氧化剂NAC组(3 mmol/L)和异乌药内酯联合NAC处理组(Isolinderalactone 15μmol/L+NAC 3 mmol/L)进行实验。采用CCK-8方法检测细胞活性,通过流式细胞术检测细胞凋亡情况,DCFH-DA法检测A549细胞内活性氧水平变化,JC-1染色后流式细胞术检测细胞内线粒体膜电位,Western blot方法检测细胞内线粒体凋亡通路相关关键蛋白表达的变化。结果表明:异乌药内酯能抑制肺癌A549细胞生长并诱导细胞凋亡,促进ROS积累,线粒体膜显著去极化,上调促凋亡蛋白Bax表达水平而下调抗凋亡蛋白Bcl-2表达水平。抗氧化剂NAC与异乌药内酯联合作用后,与异乌药内酯单独处理组相比,以上各方面的变化水平都呈现出不同程度的下降。异乌药内酯能通过诱导细胞内活性氧积累,激活线粒体凋亡途径从而促进A549细胞发生凋亡。  相似文献   

5.
目的:通过比较阿霉素(ADR)作用的视网膜色素上皮细胞(ARPE-19)和正常ARPE-19间的差异表达基因和信号通路,探究ADR治疗玻璃体视网膜增殖性疾病的潜在机制。创新点:首次运用基因芯片技术通过比较转录组学分析探究ADR促进ARPE-19细胞凋亡的机制。方法:采用磺酰罗丹明B(sulforhodamine B,SRB)比色法和碘化丙啶(PI)单染结合流式细胞术检测ADR对ARPE-19细胞的增殖抑制作用;通过基因芯片技术筛选ADR作用的ARPE-19细胞(实验组)和正常ARPE-19细胞(对照组)间的差异表达基因和相关信号通路;用JC-1染色结合流式细胞术和Bcl2/Bax蛋白表达比率检测线粒体功能;通过检测γ-H2AX、p-CHK1、 p-CHK2等蛋白表达量分析DNA的损伤和修复。结论:ADR通过启动DNA损伤反应,引起p53信号通路依赖的线粒体功能失调并激活caspase依赖的凋亡,最终导致ARPE-19细胞死亡。  相似文献   

6.
缺血预处理是指心肌反复多次短暂缺血/再灌注,对随后长时间心肌缺血/再灌注的一种保护.缺血预处理对心肌的保护机制十分复杂,一般公认为线粒体ATP敏感性钾通道(mitoKATP)是心肌缺血预处理保护机制的终末效应器之一.mitoKATP开放后可通过以下3条途径对抗心肌缺血损伤:减少线粒体膜Ca2 通道对Ca2 内流的驱动力,抑制Ca2 内流,减轻心肌细胞钙超载;保护线粒体呼吸链,减轻自由基释放引起的损伤;抑制线粒体转换孔开放,防止细胞色素C从线粒体释放,减少细胞凋亡.  相似文献   

7.
近年来 ,细胞凋亡已成为生物医学研究领域中的一个热点 ,细胞凋亡过程复杂 ,有许多因子参与其中 ,Bcl- 2蛋白家族是细胞凋亡研究中最受关注的蛋白类群 ,它是细胞凋亡信号转导的主要调节物 ,在细胞凋亡过程中发挥重要的作用。B细胞淋巴瘤 /白血病 - 2 (B -celllymphoma/leukemia- 2 ,Bcl- 2 )基因是第一个被发现的能抑制多种细胞凋亡的原癌基因 ,它是Bcl- 2蛋白家族基因的原型。Bcl- 2基因最初是从人的滤泡性B细胞淋巴瘤中分离出来的 ,通常它定位于人的第 18号染色体。Bcl - 2蛋白由 2 39个氨基酸组成 ,分子量为 2 5~2 6KD。大多数Bcl-…  相似文献   

8.
目的:阐明白藜芦醇(RSV)在猪精液冷冻保存中的应用效果及作用机制。创新点:在冷冻过程中添加RSV,观察其对猪冻后精子抗冻能力的影响,并阐明其细胞凋亡作用机理。方法:在猪精液的冷冻和解冻过程中添加1mmol/L RSV,解冻后检测精子活力、线粒体膜电位、腺苷三磷酸(ATP)含量、凋亡水平和凋亡通路中相关基因的表达情况。结论:(1)与鲜精相比,冷冻精液的活力、顶体完整性和质膜完整性均显著降低,冷冻前后RSV处理未能显著提高精子活力(0.44 vs. 0.40,P0.05),但能显著提高顶体完整性(57.65%vs. 47.00%,P0.05)和质膜完整性(46.67%vs.38.85%,P0.05)。(2)解冻后精子线粒体膜电位显著下降,RSV的添加能提高精子膜电位水平。(3)冷冻解冻过程中添加RSV能显著降低精子的活性氧(ROS)水平(58.65%vs.88.41%,P0.05),增加精子的ATP含量(0.49μmol/L vs.0.25μmol/L,P0.05)。(4)TUNEL凋亡检测后,冷冻精子的凋亡率(80.41%)与鲜精组(9.70%)相比显著增加(P0.05),RSV处理能显著降低冻精的凋亡比例(68.32%,P0.05)。(5)实时荧光定量聚合酶链反应(q RT-PCR)的结果显示,猪精液冷冻后,无论是死亡受体介导凋亡途径中的相关基因(肿瘤坏死因子α(TNF-α)、TNF受体超族配体(Fas L)和半胱氨酸的天冬氨酸蛋白水解酶8(Caspase-8)),还是线粒体介导凋亡途径中的相关基因(锰超氧化物歧化酶(Mn SOD)、B淋巴细胞瘤-2(Bcl-2)、Bcl-2相关X蛋白质(Bax)和半胱氨酸的天冬氨酸蛋白水解酶9(Caspase-9)),均产生明显变化,RSV添加亦能显著改变其表达水平。综上所述,猪精液冷冻解冻过程中RSV添加虽未能显著提高精子活力,但仍表现为抗氧化保护效果,体现在改善了线粒体功能,并通过改变死亡受体和线粒体介导的凋亡途径中相关基因的表达水平,降低了冻后精子的细胞凋亡。  相似文献   

9.
细胞凋亡是细胞在各种死亡信号刺激后发生的一系列大量激活的主动性细胞死亡过程.细胞凋亡的信号传导主要有两条途径:受体依赖途径(外部途径)和线粒体途径(内部途径),两条途径互相交叉;死亡受体、死亡配体和半胱氨酸蛋白酶等细胞凋亡因子在两条途径中起核心作用.  相似文献   

10.
一氧化氮(NO)在生物体内有多种生理和毒性作用。大量研究表明:NO参与各种原因引起的肝脏疾病,且呈现双重作用。多数学者认为高浓度的NO可促进肝脏损伤,机制与促进脂质过氧化、线粒体损伤,抑制蛋白、糖原合成等有关;而低浓度的NO具有肝保护作用,机制与抑制MPT和细胞凋亡,抑制中性粒细胞聚集,改善肝脏微循环等有关。  相似文献   

11.
Games have always been a part of the human experience. Even the earliest of civilizations created games for enjoyment and entertainment. However, the educational value of those games is a relatively recent consideration. Over the previous fifty years, scholars have questioned the potential positive lessons learned from games such as Monopoly®, Scrabble®, and sports. While millions of children participate in these activities, a new type of gaming has emerged over the previous decade and is quickly surpassing other gaming formats. Massively Multiplayer Online Role Playing Games (MMORPGS), such as World of Warcraft and Diablo, now have millions of players; however, the potential educational influence of these games is relatively unknown. This article presents an exploration of one potential educational strand – economic theory – that these types of games may facilitate.  相似文献   

12.
p16^INK4a是细胞周期负调控因子,在多种细胞的衰老过程中起着关键作用.为了研究p16^INK4a的表达对小鼠成纤维细胞即NIH3T3细胞生长增殖的影响,将真核表达载体PRetro-onpl6通过逆转录病毒介导的方法将其转染至NIH3T3细胞中,经嘌呤霉素筛选,获得整合有p16基因的稳定细胞株NIH3T3/pRetro-on-p16,并通过脱氧四环素的诱导,观察到NIH3T3/pRetro-on-p16衰老的显著特征:细胞宽大铺展、形状不规则、折射率低等,并且细胞生长速度明显减慢.  相似文献   

13.
Epstein-Barr virus(EBV),a human gammaherpesvirus carried by more than 90% of the world’s population,is associated with malignant tumors such as Burkitt’s lymphoma(BL),Hodgkin lymphoma,post-transplant lymphoma,extra-nodal natural killer/T cell lymphoma,and nasopharyngeal and gastric carcinomas in immune-compromised patients.In the process of infection,EBV faces challenges:the host cell environment is harsh,and the survival and apoptosis of host cells are precisely regulated.Only when host cells receive sufficient survival signals may they immortalize.To establish efficiently a lytic or long-term latent infection,EBV must escape the host cell immunologic mechanism and resist host cell apoptosis by interfering with multiple signaling pathways.This review details the apoptotic pathway disrupted by EBV in EBV-infected cells and describes the interactions of EBV gene products with host cellular factors as well as the function of these factors,which decide the fate of the host cell.The relationships between other EBV-encoded genes and proteins of the B-cell leukemia/lymphoma(Bcl) family are unknown.Still,EBV seems to contribute to establishing its own latency and the formation of tumors by modifying events that impact cell survival and proliferation as well as the immune response of the infected host.We discuss potential therapeutic drugs to provide a foundation for further studies of tumor pathogenesis aimed at exploiting novel therapeutic strategies for EBV-associated diseases.  相似文献   

14.
非晶硅/微晶硅叠层薄膜电池因其较高的电池效率和稳定性而具有广阔的应用前景.简单介绍了非晶硅/微晶硅叠层电池的基本工作原理,综述了影响叠层电池效率的两个关键因素:各子电池间的电流匹配和叠层电池中的N/P隧穿结以及此方面国内外的研究现状.  相似文献   

15.
In the current studies a miniature silicon wafer fuel cell (FC) using L-ascorbic acid as fuel was developed. The cell employs L-ascorbic acid and air as reactants and a thin polymer electrolyte as a separator. Inductively coupled plasma (ICP) silicon etching was employed to fabricate high aspect-ratio columns on the silicon substrate to increase the surface area. A thin platinum layer deposited directly on the silicon surface by the sputtering was used as the catalyst layer for L-ascorbic acid electro-oxidation. Cyclic voltammetry shows that the oxidation of L-ascorbic acid on the sputtered platinum layer is irreversible and that the onset potentials for the oxidation of L-ascorbic acid are from 0.27 V to 0.35 V versus an Ag/AgCl reference electrode. It is found that at the room temperature, with 1 mol/L L-ascorbic acid/PBS (phosphate buffered solution) solution pumped to the anode at 1 ml/min flow rate and air spontaneously diffusing to the cathode as the oxidant, the maximum output power density of the cell was 1.95 mW/cm^2 at a current density of 10 mA/cm^2.  相似文献   

16.
以吐温80为分散剂,分别以丙烯酰胺和N,N’-亚甲基双丙烯酰胺为单体和交联剂,制备中间相碳微球/石墨(MCMB/G)浆料,采用凝胶注模工艺,制得直接醇类燃料电池管状阴极支撑体素坯,经液态干燥、滚动干燥和埋石墨粉烧结等过程处理制得其样品。所制备的直接醇类燃料电池管状阴极支撑体物理性能为:孔隙率42.7%,电阻率0.0276Ω·cm,抗折强度6.23 MPa,抗压强度16.29 MPa,具有收缩率低、变形量小、石墨化度高、电导率高、力学性能好等特点。  相似文献   

17.
This article informs school improvement and educational change from a radically different perspective. Building upon work done recently in neural psychology, primatology and ethology, the article examines four common and general types of organisational form: the cell, the silo, the pyramidal, and the network types of organisational structures. Status and dominance hierarchies are discussed, as are the dynamics of collaboration/competition and collectivism/individualism. Final consideration is given to the concepts of culture and community, especially as they manifest in the school improvement literature.  相似文献   

18.
INTRODUCTION OF ACUTE LUNG IN- JURY/ACUTE RESPIRATORY DISTRESS SYN- DROME (ALI/ARDS) Acute lung injury (ALI) and its more severe form, the acute respiratory distress syndrome (ARDS) are syndromes of acute respiratory failure, which was defined by radiological (bilateral lung field infiltrates) and physiological (the ratio of arterial oxygen pres- sure and the inspiratory oxygen concentration, Pa O 2 /Fi O2≤300 mmHg for ALI and ≤200 mmHg for ARDS) criteria in…  相似文献   

19.
采用适用于石蜡切片的新近发展的抗体,对20例在临床病理上符合恶性组织细胞增生症(简称恶组)特点的病例进行了其细胞属性的探讨.发现大多数病例的瘤细胞为组织细胞起源的可能性大;5例肠型恶组,其中4例瘤细胞表达 T 细胞标记,表明其应归属于 T 淋巴细胞系列肿瘤;另一例肠型恶组表达组织细胞标记,可能代表真正的组织细胞源性的肠型恶组;此外,初步观察表明除肉芽肿样型外恶组的其它三种病理组织学类型间无明显免疫组化表型的不同.  相似文献   

20.
Polyunsaturated fatty acids (PUFAs) possess anti-cancer action both in vitro and in vivo. In the present study, we detected cell viability with methyl thiazolyl tetrazolium (MTT) assay and cell membrane permeability with propidium iodide (PI) fluorescence dyeing, and calculated cell membrane fluidity change as fluorescence anisotropy. Fatty acid content in cells was measured by gas chromatography/mass spectroscopy (GC/MS), and the relationship between fatty acid composition and cell viability was studied. We observed that n-6 PUFA linoleic acid (LA) inhibited tumor cell growth at high concentrations (≥300 μmol/L), while low concentrations (100–200 μmol/L) seemed to promote cell proliferation. Analyses of cell membrane permeability, cell membrane fluidity, and cell fatty acid composition suggested that the anti-cancer action of LA could be related to changes in the ratio of n-6 to n-3 PUFAs. We observed that pre-incubation of cancer cells with 100 μmol/L LA for 24 h enhanced cell sensitivity to the cytotoxic action of LA, whereas undifferentiated cell line LoVo seemed to have a distinct path in LA-induced death. These results showed that one of the mechanisms by which supplementation of LA induces cancer cell death could be altering the ratio of n-6/n-3 PUFAs, and this may be related to cell differentiation status.  相似文献   

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