端粒酶是干扰素抗肿瘤的新靶点

端粒酶(telomerase)是一种具有逆转录活性的核糖核蛋白酶.端粒酶的异常活化是细胞永生化和肿瘤形成的关键步骤. 端粒酶活性与细胞周期及细胞凋亡调控密切相关;端粒酶由端粒酶逆转录酶、端粒酶RNA、端粒酶相关蛋白质组成,端粒酶逆转录酶是端粒酶活性的决定性组分.干扰素(interferon)是一种具有抗病毒、抗增殖、抗肿瘤和免疫调节等功能的细胞因子;近年研究表明,干扰素通过相关信号转导途径而调节端粒酶活性,诱导细胞凋亡,为肿瘤的生物治疗提供了新思路;但干扰素与端粒酶活性相关的抗肿瘤机制研究尚不充分. 本文综述干扰素通过调节端粒酶逆转录酶转录因子的表达和相互作用而抑制端粒酶活性、调节细胞周期并诱导细胞凋亡等抗肿瘤作用机制.     

端粒及端粒酶的研究进展

端粒是染色体末端独特的蛋白质-DNA结构,在保护染色体的完整性和维持细胞的复制能力方面起着重要的作用.端粒酶则是由RNA和蛋白质亚基组成的、能够延长端粒的一种特殊反转录酶.端粒长度和端粒酶活性的变化与细胞衰老和癌变密切相关.端粒结合蛋白可能通过调节端粒酶的活性来调节端粒长度,进而控制细胞的衰老、永生化和癌变.研制端粒酶的专一性抑制剂在肿瘤治疗方面有着广阔的前景.     

依赖端粒酶的端粒维持机制

端粒是真核生物染色体的末端重要结构复合物,对维持染色体稳定性起着重要作用。端粒酶的主要功能是复制端粒末端DNA,维持端粒长度。端粒酶活性调节与肿瘤发生和细胞衰老有着密切关系。本简要综述近年来依赖端粒酶的端粒维持机理的研究进展。     

端粒和端粒酶及其在肝细胞癌中的研究进展

摘要：端粒是位于染色体末端的特殊核蛋白复合物,其高度保守的重复序列和蛋白复合物形成保护环结构,以维持线性染色体的稳定性和完整性。端粒酶通过添加富含鸟嘌呤的重复序列,在维持和调节端粒长度、细胞永生性和衰老中起着重要作用。通过研究病变细胞的端粒长度变化趋势和端粒酶活性,可为选择端粒酶作为治疗癌症的标记物提供理论参考。本文针对端粒、端粒酶的结构和日常作用机理,以及它们在肝细胞癌中的研究进展进行综述,以期有助于恶性肿瘤和代谢性疾病的预防、诊断和治疗。     

铅和硒对端粒长度、端粒酶及端粒结合蛋白的影响

以酿酒酵母细胞为实验材料 ,在分子水平上研究铅 (Pb)和硒 (Se)对端粒长度、端粒酶及端粒结合蛋白的影响。结果发现 :与对照组相比 ,添加 1mg/LPb的培养基中培养 10 0代后的酿酒酵母细胞中端粒DNA的平均长度缩短 ,端粒结合蛋白Rap1p含量减少 ,而且Rap1p蛋白的二级结构受到扰动、端粒酶活性降低、43%的细胞死亡。加 1mg/LSe培养 10 0代后的酿酒酵母细胞与对照组相比 ,细胞中端粒平均长度增加 ,Rap1p蛋白浓度和二级结构保持稳定 ,端粒酶活性增加 ,细胞正常存活。以上结果表明 ,Pb对酿酒酵母细胞端粒有损伤 ,而且其损伤在子代细胞中有累积效应 ;而Se对Pb损伤具有一定程度的修复保护作用 ,适量给机体补Se对抑制细胞损伤和衰老有一定作用。由于端粒的特殊结构特征 ,推断Pb和Se是通过作用于端粒酶及端粒结合蛋白而间接影响端粒长度的     

端粒生物学与肿瘤治疗

端粒的生物学功能主要是保护染色体末端,避免核酸酶对染色体末端的降解,防止染色体之间发生融合和重排。大多数人类肿瘤细胞通常通过端粒酶活性的重新激活来延长端粒,从而稳定染色体端粒DNA的长度。端粒酶是由端粒酶逆转录酶和端粒酶RNA模板组成的具有特殊逆转录活性的核糖核蛋白复合物。抑制端粒酶阳性细胞中的端粒酶活性会导致细胞凋亡或衰老。目前有多种以端粒和端粒酶为靶点来进行肿瘤治疗的策略。     

端粒与端粒酶的研究——解读2009年诺贝尔生理学或医学奖

三位美国科学家(Elizabeth H. Blackburn, Carol W. Greider 和Jack W. Szostak)因发现“端粒和端粒酶是如何保护染色体的”获得了2009年的诺贝尔生理学或医学奖．端粒是染色体末端的特殊结构,对染色体有保护作用,而端粒酶能合成端粒,使得端粒的长度和结构得以稳定．研究发现,端粒长度和端粒酶活性与细胞的寿命以及很多疾病发生直接相关．随着研究的不断深入,实现合理控制端粒的长度和端粒酶活性成为可能,这将有助于攻克医学领域“癌症、特定遗传病和衰老”三个重要领域的难题,有望研究开发出潜在的新疗法．     

端粒酶的非端粒保护作用

端粒酶与细胞永生化和肿瘤的发生发展密切相关,过去认为是由于端粒酶保护端粒从而阻止因端粒缩短所导致的细胞凋亡;然而近年来,越来越多证据表明:端粒酶在维持端粒长度之外,还存在着非端粒保护作用。通过对其非端粒保护作用的研究,有助于深入而全面地阐明端粒酶的生物学行为及其作用机理,对于肿瘤等疾病的治疗具有重要意义。本文对端粒酶的非端粒保护作用进行小结。     

Embryo and Endosperm Function and Failure inSolanumSpecies and Hybrids

Although the importance of the endosperm as a food store inmany angiosperm seeds is well known, its significance duringearly embryogenesis has been neglected. In many interspecifichybrids, and in some other situations, embryos do not developfully and abort. It has often been stated that this is causedby the endosperm failing to conduct sufficient nutrients tothe embryo, but seldom has it been suggested that the endospermactively controls most of the early stages of morphogenesisof the embryo. Information gleaned from a broad survey of theliterature, combined with additional evidence presented here,obtained fromSolanum incanumand interspecific hybrids, indicatethat the endosperm is dynamic and very active in regulatingearly embryo development. This requires highly integrated geneticcontrol of rapidly changing metabolism in the endosperm. Ininterspecific hybrids, lack of coordination may cause unbalancedproduction of growth regulating substances by the endospermand hence abortion of the embryo, or even unregulated productionof nucleases and proteases resulting firstly in autolysis ofthe endosperm and then digestion of the embryo. The endospermmay thus serve to detect inappropriate hybridization of speciesor ploidy levels and so prevent waste of resources by producingseeds that would result in sterile hybrids or unthrifty subsequentgenerations. This discriminatory function of the endosperm hasdiminished during evolution and domestication of the crop plantSolanummelongenaL.Copyright 1998 Annals of Botany Company Solanum, embryo morphogenesis, endosperm, hybrid, seed development.     

环腺苷酸应答元件结合蛋白与学习记忆

环腺苷酸(cAMP)应答元件结合蛋白(cAMP response element binding protein,CREB)是一种核转录因子,可与cAMP反应元件结合,调节基因转录,具有调节精子生成,昼夜节律,学习记忆等功能.近年来关于其在学习记忆中的作用成为医学研究热点.CREB是神经元内多条信息传递途径的汇聚点,参与长时记忆形成和突触可塑性.长时记忆(long-term memory)形成需依赖CREB介导的基因转录,干扰或抑制CREB活性可破坏长时记忆.长时程增强(long-term potentiation,LTP)是研究学习记忆的理想模型,在LTP诱导和维持过程中均可观察到CREB活性持续升高.但增龄过程中,海马CREB活性下降,影响学习记忆功能,与许多神经退行性疾病发生有关.     

HIFs and tumors--causes and consequences

For most organisms oxygen is essential fo life. When oxygen levels drop below those required to maintain the minimum physiological oxygen requirement of an organism or tissue it is termed hypoxia. To counter act possible deleterious effects of such a state, an immediate molecular response is initiated causing adaptation responses aimed at cell survival. This response is mediated by the hypoxia-inducible factor-1 (HIF-1), which is a heterodimer consisting of an alpha- and a beta-subunit. HIF-1 alpha protein is stabilized under hypoxic conditions and therefore confers selectivity to this response. Hypoxia is characteristic of tumors, mainly because of impaired blood supply resulting from abnormal growth. Over the past few years enormous progress has been made in the attempt to understand how the activation of the physiological response to hypoxia influences neoplastic growth. In this review some aspects of HIF-1 pathway activation in tumors and the consequences for pathophysiology and treatment of neoplasia are discussed.     

Pragmatic Women and Body Politics and Maternities and Modernities: Colonial and Postcolonial Experiences in Asia and the Pacific

Pragmatic Women and Body Politics. Margaret Lock and Patricia A. Kaufert. eds. Cambridge, UK: Cambridge University Press, 1998. xii +364 pp.
Maternities and Modernities: Colonial and Postcolonial Experiences in Asia and the Pacific. Kalpana Ram and Margaret Jolly. eds. Cambridge, UK: Cambridge University Press, 1998. xiv. 305 pp.