检索结果-内蒙古大学图书馆

浙江大学学报（医学版） 2015年第3期44卷 323-328页

作者：杨敏丽叶招明浙江大学医学院附属第二医院理疗科浙江杭州310009 浙江大学医学院附属第二医院骨科浙江杭州310009

目的：探索极低频电磁场对人骨肉瘤细胞增殖凋亡的影响及其分子机制。方法：采用50 Hz、1 mT 的极低频电磁场作用于人骨肉瘤细胞MG－63，通过MTT法检测MG－63细胞的存活率，通过流式细胞术检测MG－63细胞的凋亡率及活性氧水平，并检测 M... 详细信息

目的：探索极低频电磁场对人骨肉瘤细胞增殖凋亡的影响及其分子机制。方法：采用50 Hz、1 mT 的极低频电磁场作用于人骨肉瘤细胞MG－63，通过MTT法检测MG－63细胞的存活率，通过流式细胞术检测MG－63细胞的凋亡率及活性氧水平，并检测 MG－63细胞给予活性氧抑制剂 N－乙酰半胱氨酸（ NAC ）及p38 MAPK抑制剂SB203580作用后细胞凋亡率的变化；通过蛋白质印迹法检测极低频电磁场处理及NAC干预后MG－63细胞p38 MAPK蛋白水平。结果：极低频电磁场能够显著抑制MG－63细胞的存活率，诱导MG－63细胞凋亡及活性氧生成；给予2．5 mmol／L NAC或SB203580干预后MG－63细胞凋亡率显著下降；极低频电磁场处理MG－63细胞后胞内p38 MAPK表达增多，而NAC干预后磷酸化p38 MAPK减少。结论：极低频电磁场可诱导人骨肉瘤细胞MG－63凋亡，其机制可能与活性氧生成增加、p38 MAPK激活有关。

关键词：电磁场细胞凋亡/辐射效应辐射损伤骨肉瘤/病理学细胞系肿瘤/辐射效应 p38丝裂原活化蛋白激酶类活性氧

来源：评论

学校读者我要写书评

暂无评论

放射诱导的六株细胞系细胞周期和细胞凋亡变化的观察

引用

中华肿瘤防治杂志 2008年第13期15卷 988-990,995页

作者：刘沙董广璐刘伟金茜张淑云郑淑香邢丽娜哈尔滨医科大学附属第二医院肿瘤放射治疗科黑龙江哈尔滨150086 哈尔滨医科大学附属第二医院肿科研实验中心黑龙江哈尔滨150086

目的:探讨放射诱导的6株细胞系细胞周期和细胞凋亡的变化特点。方法:正常肝细胞系HL-7702,肝癌细胞系HepG2和SMMC-7721,肺小细胞癌HCI-H460,肺腺癌A549和宫颈癌细胞系Hela常规培养48h后接受4GyX射线照射;收获受照前(0h)和受照后6、12、2... 详细信息

目的:探讨放射诱导的6株细胞系细胞周期和细胞凋亡的变化特点。方法:正常肝细胞系HL-7702,肝癌细胞系HepG2和SMMC-7721,肺小细胞癌HCI-H460,肺腺癌A549和宫颈癌细胞系Hela常规培养48h后接受4GyX射线照射;收获受照前(0h)和受照后6、12、24、36和48h的细胞,采用流式细胞术(FCM)检测各细胞系细胞凋亡和细胞周期。结果:在4GyX线照射前,SMMC-7721和HCI-H460细胞凋亡率明显高于其他4株细胞系,两者差异有统计学意义(t=20.98,P<0.005);在照射后12h,与照射前相比6株细胞系细胞凋亡率均有显著增加(t=5.27,P<0.05),SMMC-7721、HCI-H460和A549同时伴有S期和G2～M期细胞比率的降低;在照射后36hHCI-H460出现第2个细胞凋亡峰,伴有极低比例的S期和G2～M期细胞;HepG2在照射后12h、HL-7702和Hela在照射后24h均有明显的G2/M期阻滞。结论:4GyX线诱导的细胞凋亡主要发生在射线照射后12～36h,6株细胞系可能均发生了"有丝分裂前凋亡";每株细胞还呈现了不同的细胞凋亡和细胞周期变化特点,具有组织细胞特异性。

关键词：肿瘤/放射疗法细胞凋亡/辐射效应肿瘤细胞培养的细胞周期

来源：评论

学校读者我要写书评

暂无评论

OA护膝防治膝骨性关节炎的实验研究

OA护膝防治膝骨性关节炎的实验研究

引用

作者：林木南福建中医学院

学位级别：博士

目的研制OA护膝,并通过观察OA护膝对骨性关节炎细胞因子、基质溶解素、透明质酸、氧自由基代谢、关节软骨宏微观结构变化和细胞增殖、凋亡的影响,探讨其防治膝骨性关节炎的机制及疗效。方法1 OA护膝的研制:根据中医“寒者热之”、“瘀... 详细信息

目的研制OA护膝,并通过观察OA护膝对骨性关节炎细胞因子、基质溶解素、透明质酸、氧自由基代谢、关节软骨宏微观结构变化和细胞增殖、凋亡的影响,探讨其防治膝骨性关节炎的机制及疗效。方法 1 OA护膝的研制:根据中医“寒者热之”、“瘀者通之”的治则,以PIC16F630单片机为核心,电路主要由升压、输出、单片机控制以及电热软膜4部分组成,通过键盘设定单片机产生不同幅度和频率的动态变频疏密波进行治疗,30min后单片机内部定时器中断,自动关机。 2实验研究:日本大耳白兔60只,随机分为2组,即:正常组(10只)和手术组(50只)。采用改良Hulth法复制膝骨性关节炎模型,术后随机分为5组,即模型组、对照组(微波组)、实验1组(电组)、实验2组(热组)、实验3组(护膝组),并行对应治疗。8周后,分别测定关节滑液IL-1β、IL-6、TNF-α、MMP-3、HA浓度,及血液MDA、SOD、NO浓度。16周后,分别测定关节滑液IL-1β、IL-6、TNF-α、MMP-3、HA浓度,关节滑膜及血液MDA、SOD、NO浓度,并用CR片、光镜、透射电镜、Tunel法、PCNA进行组织形态学观察,同时用RT-PCR检测关节软骨细胞Bcl-2、P53的mRNA相对表达水平。结果 1 OA护膝的研制:护膝输出的疏密波可控制由2～300Hz不同频率刺激脉冲组成,脉冲宽度在100～150μs之间,输出正负向对称的刺激脉冲,采用可充电的手机电池(3.7V)供电,单片机定时,30min自动关机。电热软膜工作时的温度控制在40℃左右。 2实验研究:模型组、对照组、实验1组、实验2组、实验3组关节液中IL-1β、IL-6、TNF-α、MMP-3、血液MDA、NO浓度均高表达,含量16周明显高于8周时,而关节液HA和血液SOD浓度均低表达,含量16周明显低于8周时,16周时关节滑膜中MDA、NO浓度、关节软骨细胞P53的mRNA相对表达水平、AI均呈高表达,而SOD浓度、关节软骨细胞Bcl-2的mRNA相对表达水平、PI均低表达,与正常组有显著性差异(P＜0.01,P＜0.05)。8周时,关节液中IL-1β、IL-6、TNF-α、MMP-3、HA,血液中MDA、NO、SOD含量,对照组、实验1组、实验2组、实验3组与模型组有显著性差异(P＜0.01,P＜0.05):对照组、实验1组、实验2组与实验3组有显著性差异(P＜0.05)。16周时,关节液中IL-1β、IL-6、TNF-α、MMP-3、HA,血液和关节滑膜中MDA、NO、SOD含量,关节软骨细胞Bcl-2、P53的mRNA相对表达水平,AI、PI,对照组、实验1组、实验2组、实验3组与模型组有显著性差异(P＜0.01,P＜0.05);对照组、实验1组、实验2组与实验3组有显著性差异(P＜0.05)。16周时与8周时,关节液中IL-1β、IL-6、TNF-α、MMP-3、HA,血液中MDA、NO、SOD含量,实验3组间比较有显著性差异(P＜0.05)。CR片显示:正常组关节间隙正常,关节面平整光滑,无骨赘;模型组内侧间隙明显变窄,有明显骨赘;光镜显示:正常组关节软骨四层结构清晰可辨,软骨细胞排列整齐呈柱状,染色质分布均匀,细胞核清晰;模型组关节软骨层变薄,部分区域软骨细胞核固缩、坏死,软骨细胞排列紊乱,四层结构不易分辨;电镜显示正常组软骨细胞呈椭圆形,细胞及胞膜完整,包质内可见丰富粗面内质网、高尔基体、线粒体,细胞核完整,染色质分布均匀;模型组软骨细胞明显固缩且外形不规则,细胞周晕消失,胞浆内细胞器凝成高电子密度的片状物不易分辨,细胞核不规则,染色质浓聚,散裂于核中;实验3组内侧间隙变窄,关节边缘有轻微骨赘,关节面粗糙变形,软骨细胞轻度萎缩,核内异染色质增多,胞质内可见脂滴及微丝出现。对照组、实验1组与实验2组介于模型组、实验3组之间。免疫组化观察结果:正常组、实验3组、实验1组、实验2组、对照组、模型组TUNEL阳性率逐渐增高,PCNA阳性率逐渐降低。结论 1以PIC16F630单片机为系统控制核心的OA护膝,可通过键盘按钮控制输出信号的频率、脉冲宽度、强度和工作时间。 2 OA护膝采用低频温热动态变频疏密波,针对膝OA病理过程中的多个环节进行调节,能有效抑制细胞因子、MMP—3、HA、氧自由基、NO的生物学效应,增强SOD的生物学活性,提高关节软骨细胞Bcl-2mRNA表达,减弱软骨细胞P53mRNA表达,从而抑制软骨细胞凋亡,延缓膝关节软骨宏观形态、软骨细胞及软骨基质的退变。

关键词：骨关节炎,膝/中医疗法白细胞介素类基质溶解素-3 活性氧/代谢软骨,关节/病理学基因,Bcl-2/辐射效应蛋白质P53 细胞凋亡/辐射效应 @护膝

来源：评论

学校读者我要写书评

暂无评论

极低频电磁场诱导人骨肉瘤细胞凋亡及其机制研究

极低频电磁场诱导人骨肉瘤细胞凋亡及其机制研究

引用

作者：杨敏丽浙江大学

学位级别：硕士

研究目的：探索极低频电磁场(ELF-EMF)对人骨肉瘤细胞增殖凋亡的影响,并研究其分子机制。研究方法：通过MTT法研究50Hz, 1mT的ELF-EMF对人骨肉瘤细胞MG-63、MNNG-HOS Cl的增殖作用；通过流式细胞术检测5OHz, 1mT ELF-EMF处理人骨肉瘤细... 详细信息

研究目的：探索极低频电磁场(ELF-EMF)对人骨肉瘤细胞增殖凋亡的影响,并研究其分子机制。研究方法：通过MTT法研究50Hz, 1mT的ELF-EMF对人骨肉瘤细胞MG-63、MNNG-HOS Cl的增殖作用；通过流式细胞术检测5OHz, 1mT ELF-EMF处理人骨肉瘤细胞不同时间后细胞凋亡率、活性氧(ROS)水平以及给予活性氧抑制剂N-乙酰半胱氨酸(NAC)及p38MAPK抑制剂SB203580作用后细胞凋亡率的变化；通过蛋白质免疫印迹法检测50Hz, 1mT ELF-EMF处理人骨肉瘤细胞MG-63、MNNG-HOS Cl不同时间后及NAC干预后MAPK信号通路相关蛋白变化。研究结果：ELF-EMF够显著抑制人骨肉瘤细胞的增殖,处理3h后细胞存活率仅20%,且这种效应呈明显的时间依赖性；ELF-EMF可诱导人骨肉瘤细胞凋亡及促进ROS水平上升,给予2.5mM NAC干预后人骨肉瘤细胞凋亡率显著下降；ELF-EMF处理入骨肉瘤细胞后其胞内MAPKp38激活,磷酸化p38MAPK蛋白表达增多,而NAC干预后其磷酸化水平明显下降。此外,p38MAPK抑制剂SB203580干预后人骨肉瘤细胞凋亡亦显著下降。研究结论：ELF-EMF通过上调ROS激活MAPKp38信号通路,进而诱导人骨肉瘤细胞凋亡,抑制其生长。

关键词：电磁场细胞凋亡/辐射效应辐射损伤骨肉瘤/病理学细胞系肿瘤/辐射效应 p38丝裂原活化蛋白激酶类活性氧

来源：评论

学校读者我要写书评

暂无评论

Dose and dose-rate effects of X rays and fission neutrons on lymphocyte apoptosis in p53(+/+) and p53(-/-) mice

引用

JOURNAL OF RADIATION RESEARCH 2000年第2期41卷 113-127页

作者： Fujikawa, K Hasegawa, Y Matsuzawa, S Fukunaga, A Itoh, T Kondo, S Kinki Univ Atom Energy Res Inst Higashiosaka Osaka 5778502 Japan Osaka City Univ Coll Nursing Osaka 5450051 Japan

Following the exposure of mice to X rays or fission neutrons, the frequency (F) of apoptosis was measured after 4 h, and the weight loss or lymphocyte content loss in the thymus and spleen was measured after 24 h. In p53(+/+) mice, F increased linearly with the dose (D (Gy)) and the induced rate per Gy of F (detected by TUNEL staining) was 0.05 and 0.23 for X rays and fission neutrons, respectively. Therefore, the RBE of fission neutrons was 4.6 for apoptosis induction. This indicates that radiation-induced apoptosis is mostly due to double strand breaks (DSBs) in DNA because we previously obtained almost the same RBE value of fission neutrons for the induction of crossover mutations in Drosophila melanogaster, which arise from the recombinational repair of DSBs. In p53(+/+) mice, decreases in the organ weight and the lymphocyte content were observed for the thymus and the spleen 24 h after X-irradiation. These atrophic changes in the thymus and the spleen quantitatively corresponded to the total apoptotic cell deaths occurring in them. However, in p53(-/-) mice, no vigorous apoptosis was induced after X-irradiation, and hyperplastic changes in the weight and the lymphocyte content appeared in the thymus and the spleen 24 h after X-irradiation. In p53(+/+) mice, there was no difference in the induced rate per Gy of reduction in the surviving fraction of lymphocytes between acute (0.4 Gy/min) and chronic (3 mGy/min) gamma-irradiations. Namely, radiation-induced apoptosis in lymphocytes is a dose-rate independent event.

关键词：细胞凋亡/遗传学细胞凋亡/辐射效应萎缩 DNA损伤剂量效应关系辐射快中子 γ射线基因 p53 淋巴细胞计数淋巴细胞/细胞学淋巴细胞/辐射效应小鼠近交C57BL 小鼠近交ICR 小鼠基因敲除器官测量/辐射效应器官特异性辐射损伤实验性/病理学辐射耐受性/遗传学相对生物学效应脾/病理学脾/辐射效应胸腺/病理学胸腺/辐射效应肿瘤抑制蛋白质p53/缺乏肿瘤抑制蛋白质p53/生理学体重减轻/辐射效应 X线动物女(雌)性小鼠

来源：评论

学校读者我要写书评

暂无评论

Optimization of single-cell gel electrophoresis (SCGE) for quantitative analysis of neuronal DNA damage

引用

BIOTECHNIQUES 1999年第2期26卷 282-+页

作者： Morris, EJ Dreixler, JC Cheng, KY Wilson, PM Gin, RM Geller, HM Univ Med & Dent New Jersey Robert Wood Johnson Med Sch Dept Pharmacol Piscataway NJ 08854 USA

Neuronal death can be induced by DNA-damaging agents and occurs by apoptosis involving a specific signal-transduction pathway. However, to our knowledge, methods for the quantitative determination of DNA damage in individual neurons have trot yet been described. Here we optimize the single-cell gel electrophoresis (SCGE) or "comet"-assay to measure DNA damage,within individual neurons growing in dissociated cell culture. In addition, Mle have,written a macro for the NIH Image program to determine the tail moment of individual comets. We have calibrated this method using gamma-irradiated (0-16 Gy) cerebral cortical neurons from the rat central nervous system. Neuronal DNA damage (in the form of DNA strand breaks) occurs in a linear;dose-dependent manner, which can be quantitatively determined in. vitro using the SCGE assay. These data demonstrate that the SCGE assay is an effective method to measure DNA damage in individual neurons and may be highly useful for the study of neuronal DNA damage formation, repair and apoptosis.

关键词：细胞凋亡/遗传学细胞凋亡/辐射效应细胞分裂/辐射效应细胞培养的大脑皮质/细胞学 DNA损伤 DNA修复电泳琼脂凝胶/方法电泳琼脂凝胶/标准神经元/细胞学神经元/生理学结果可重复性动物大鼠

来源：评论

学校读者我要写书评

暂无评论

Sensitization by wortmannin of heat- or X-ray induced cell death in cultured Chinese hamster V79 cells

引用

JOURNAL OF RADIATION RESEARCH 2000年第2期41卷 93-102页

作者： Tomita, M Suzuki, N Matsumoto, Y Hirano, K Umeda, N Sakai, K Univ Tokyo Grad Sch Med Dept Radiat Oncol Bunkyo Ku Tokyo 1130033 Japan Tokyo Univ Pharm & Life Sci Sch Life Sci Tokyo 1920392 Japan

Here we found that wortmannin sensitized Chinese hamster V79 cells to hyperthermic treatment at 44.0 degrees C as determined either by colony formation assay or by dye exclusion assay. Wortmannin enhanced heat-induced cell death accompanying cleavage of poly (ADP-ribose) polymerases (PARP). Additionally, the induction of heat shock protein HSP70 was suppressed and delayed in wortmannin-treated cells. Heat sensitizing effect of wortmannin was obvious at more than 5 or 10 mu M of final concentrations, while radiosensitization was apparent at 5 mu M. Requirement for high concentration of wortmannin, i.e., order of mu M, suggests a possible role of certain protein kinases, such as DNA-PK and/ or ATM among P13-kinase family. The sensitization was minimal when wortmannin was added at the end of heat treatment. This was similar to the case of X-ray. Since heat-induced cell death and PARP cleavage preceded HSP70 induction phenomenon, the sensitization to the hyperthermic treatment was considered mainly caused by enhanced apoptotic cell death rather than secondary to suppression or delay by wortmannin of HSP70 induction. Further, in the present system radiosensitization by wortmannin was also at least. partly mediated through enhancement of apoptotic cell death.

关键词：雄二烯类/药理学细胞凋亡/药物作用细胞凋亡/辐射效应印迹法蛋白质半胱氨酸天冬氨酸蛋白酶/代谢细胞周期蛋白质类细胞存活细胞培养的/药物作用细胞培养的/代谢细胞培养的/辐射效应集落形成单位测定仓鼠亚科仓鼠属 DNA修复/药物作用 DNA活化蛋白激酶 DNA结合蛋白质类成纤维细胞/药物作用成纤维细胞/代谢成纤维细胞/辐射效应基因表达调控/药物作用 HSP90热休克蛋白质类/生物合成 HSP90热休克蛋白质类/遗传学热温度肺磷酸肌醇3-激酶类/拮抗剂和抑制剂磷酸肌醇3-激酶类/生理学聚ADP核糖聚合酶类/代谢蛋白质丝氨酸苏氨酸激酶/拮抗剂和抑制剂蛋白质丝氨酸苏氨酸激酶/生理学辐射增敏药/药理学肿瘤抑制蛋白质类动物

来源：评论

学校读者我要写书评

暂无评论

DNA excision repair and DNA damage-induced apoptosis are linked to poly(ADP-ribosyl)ation but have different requirements for p53

引用

MOLECULAR AND CELLULAR BIOLOGY 2000年第18期20卷 6695-6703页

作者： Beneke, R Geisen, C Zevnik, B Bauch, T Müller, WU Küpper, JH Möröy, T Univ Essen Gesamthsch Klinikum Inst Zellbiol Tumorforsch IFZ D-45122 Essen Germany Univ Essen Gesamthsch Klinikum Inst Med Strahlenbiol D-45122 Essen Germany Univ Tubingen Klinikum Inst Pathol D-72076 Tubingen Germany

Poly(ADP-ribose) polymerase (PARP) is a DNA binding zinc finger protein that catalyzes the transfer of;ADP-ribose residues from NAD(+) to itself and different chromatin constituents, forming branched ADP-ribose polymers. The enzymatic activity of PARP is induced upon DNA damage and the PARP protein is cleaved during apoptosis, which suggested a role of PARP in DNA repair and DNA damage-induced cell death. We have generated transgenic mice that lack PARP activity in thymocytes owing to the targeted expression of a dominant negative form of PARP. In the presence of single-strand DNA breaks, the absence of PARP activity correlated with a strongly increased rate of apoptosis compared to cells with intact PARP activity. We found that blockage of PARP activity leads to a drastic increase of p53 expression and activity after DNA damage and correlates with an accelerated onset of Fax expression. DNA repair is almost completely blocked in PARP-deficient thymocytes regardless of p53 status. We found the same increased susceptibility to apoptosis in PARP null mice, a similar inhibition of DNA repair kinetics, and the same upregulation of p53 in response to DNA damage. Thus, based on two different experimental in vivo models, we identify a direct, p53-independent, functional connection between poly(ADP-ribosyl)ation and the DNA excision repair machinery. Furthermore, we propose a p53-dependent link between PARP activity and DNA damage-induced cell death.

关键词：细胞凋亡/药物作用细胞凋亡/辐射效应细胞系 DNA损伤 DNA修复小鼠近交C3H 小鼠近交C57BL 小鼠转基因聚腺苷二磷酸酯核糖/代谢聚ADP核糖聚合酶类/遗传学聚ADP核糖聚合酶类/代谢聚ADP核糖聚合酶类/生理学胸腺/细胞学肿瘤抑制蛋白质p53/遗传学肿瘤抑制蛋白质p53/代谢肿瘤抑制蛋白质p53/生理学动物女(雌)性人类男(雄)性小鼠

来源：评论

学校读者我要写书评

暂无评论

ATM protein is required for radiation-induced apoptosis and acts before mitochondrial collapse

引用

INTERNATIONAL JOURNAL OF RADIATION BIOLOGY 2000年第6期76卷 841-851页

作者： Vit, JP Moustacchi, E Rosselli, F Inst Rech Sci Canc CNRS UPR42 F-94801 Villejuif France Inst Curie Rech Commiss Energie Atom CNRS UMR 218LRC 1 F-75248 Paris 05 France

Purpose: To define the role of the ataxia telangiectasia (A-T) mutated gene (ATM) in activation and progress of apoptosis. Material and methods: Three normal and three A-T EBV-transformed cell lines were studied. Following irradiation (IR), Fas activation or ceramide exposure, viability and apoptosis were measured by trypan blue dye exclusion assay and as sub-G1 cell fraction by flow cytometric analysis of propidium iodide stained cultures, respectively. Activation of caspase-3 was evaluated by immunoblot and by an in vitro activity assay on cytosolic cell extracts. To assess changes in mitochondrial potential and reactive oxygen species, cells were stained by 3,3'-dihexyloxacarbocynine iodide or hydroethidine, respectively, and scored by flow cytometry. Results: The observations establish that A-T cells are equipped with a proficient apoptotic machinery, as demonstrated by their ability to undergo mitochondrial collapse and caspase-3 activation after Fas activation or ceramide treatment. Both treatments have a similar cytotoxic effect on normal and A-T cells. In contrast, in spite of the: stronger cytotoxicity induced by IR exposure, irradiated A-T cells are unable to undergo mitochondrial collapse and caspase-3 activation. Conclusions: The data indicate that ATM is necessary in the initiation of molecular pathway(s) leading to HR-induced apoptosis, and suggest that increased radiosensitivity of A-T cells is more likely a direct consequence of necrotic cell death.

关键词：细胞凋亡/遗传学细胞凋亡/生理学细胞凋亡/辐射效应共济失调性毛细血管扩张/遗传学共济失调性毛细血管扩张/代谢共济失调性毛细血管扩张/病理学半胱氨酸天冬氨酸蛋白酶3 半胱氨酸天冬氨酸蛋白酶/代谢细胞周期蛋白质类细胞系细胞系转化 DNA结合蛋白质类酶激活/辐射效应线粒体/代谢线粒体/辐射效应聚ADP核糖聚合酶类/代谢蛋白质丝氨酸苏氨酸激酶/遗传学蛋白质丝氨酸苏氨酸激酶/代谢肿瘤抑制蛋白质类人类

来源：评论

学校读者我要写书评

暂无评论

Inhibition of proliferation and apoptosis by the transcriptional repressor Mad1 -: Repression of Fas-induced caspase-8 activation

引用

JOURNAL OF BIOLOGICAL CHEMISTRY 2000年第14期275卷 10413-10420页

作者： Gehring, S Rottmann, S Menkel, AR Mertsching, J Krippner-Heidenreich, A Lüscher, B Hannover Med Sch Inst Mol Biol D-30625 Hannover Germany

Mad1 is a member of the Myc/Max/Mad network of transcriptional regulators that play a central role in the control of cellular behavior. Mad proteins are thought to antagonize Myc functions at least in part by repressing gene transcription. To systematically examine the function of Mad1 in growth control and during apoptosis, we have generated U2OS cell clones that express Mad1 under a tetracyline-regulatable promoter (UTA-Mad1). Mad1 was induced rapidly and efficiently, localized to the nucleus, and bound to DNA as a heterodimer with Max. The induction of Mad1 reduced cellular growth and, more profoundly, inhibited colony formation of UTA-Mad1 cells. Conditioned medium neutralized this inhibitory effect implying that Mad1 function is regulated by extracellular signals. In addition Mad1 interfered with Fas-, TRAIL-, and UV-induced apoptosis, which coincided with a reduced activation of caspase-8 during Fas-mediated apoptosis in response to Mad1 expression. Furthermore, microinjection of Mad1-expressing plasmids into fibroblasts inhibited apoptosis induced by the oncoproteins c-Myc and E1A. Thus, Mad1 not only interferes with cellular proliferation but also with apoptosis, which defines a novel aspect of Mad1 function.

关键词： 3T3细胞细胞凋亡/生理学细胞凋亡/辐射效应凋亡调节蛋白质类 COS细胞载体蛋白质类半胱氨酸天冬氨酸蛋白酶8 半胱氨酸天冬氨酸蛋白酶9 半胱氨酸天冬氨酸蛋白酶/遗传学细胞集合细胞周期蛋白质类细胞分裂/生理学细胞分裂/辐射效应细胞系成纤维细胞基因表达调控/药物作用膜糖蛋白类/生理学核蛋白质类癌基因磷蛋白类/遗传学磷蛋白类/代谢重组蛋白质类/代谢阻遏蛋白质类/遗传学阻遏蛋白质类/代谢 TNF相关凋亡诱导配体四环素/药理学转录遗传/药物作用转染肿瘤细胞培养的肿瘤坏死因子α/生理学紫外线动物人类小鼠

来源：评论

学校读者我要写书评

暂无评论

建议与咨询留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

时间限定

文献类型

馆藏选择

核心期刊

语言

文献类型

帮助

文字说明：

检索规则说明：

检索范例：

分类表

所选分类

限定检索结果

文献类型

馆藏范围

日期分布

学科分类号

主题

机构

作者

语言

请选择保存的检索档案：

请选择收藏分类：

通借通还

建议与咨询 留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

时间限定

文献类型

馆藏选择

核心期刊

语言

文献类型

帮助

文字说明：

检索规则说明：

检索范例：

分类表

所选分类

限定检索结果

文献类型

馆藏范围

日期分布

学科分类号

主题

机构

作者

语言

请选择保存的检索档案： 新增检索档案 确定 取消

请选择收藏分类： 新增自定义分类 确定 取消

通借通还

建议与咨询留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

请选择保存的检索档案：

请选择收藏分类：