端粒及端粒酶

端粒和端粒酶是近年来生命科学研究的热点问题之一 .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     

端粒及端粒酶

端粒和端粒酶是近年来生命科学研究的热点问题之一，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与癌变密切相关。     

端粒缺陷相关因子和人类IgA肾病的关系(英文)

研究目的:分析在中国人群中,端粒缩短以及相关衰老因子与人类IgA肾病发生进展的关系。创新要点:目前的研究发现,端粒功能缺陷是限制分裂增殖、细胞衰老的重要分子机制。它不仅仅与衰老相关,而且在疾病的发生、进展过程中都有直接影响。肾脏的正常衰老过程伴随端粒逐渐缩短,端粒功能缺陷可以加速慢性肾脏疾病进程,并伴随相关衰老因子cathelin相关抗菌肽(CRAMP)、延长因子-1α(EF-1α)、几丁质酶(chitinase)和微管不稳定蛋白(stathmin)等表达增加。本项研究首次在中国人群中,揭示端粒缩短以及相关衰老因子与人类IgA肾病发生进展的关系。研究方法:采用双盲法,以IgA肾病患者(n=177)为实验组,以狼疮肾炎(n=50)、糖尿病肾病(n=30)和局灶节段性肾小球硬化(n=30)病人以及健康人(n=83)为对照组,通过定量荧光原位杂交(qFISH)检测了肾脏组织的端粒长度,并通过酶联免疫吸附试验(ELISA)检测了血液、尿液中的CRAMP、EF-1α、stathmin的含量,运用几丁质酶试剂盒(CS1030)检测了血液、尿液中几丁质酶的酶活性,运用免疫荧光染色检测了组织中CRAMP的表达情况。重要结论:端粒缩短和相关炎症蛋白与IgA肾病的发生发展有关,并为IgA肾病的特异性诊断和及预后评估提供可靠的研究基础。     

端粒结合蛋白与端粒长度的调节机制

端粒酶是位于真核细胞线性染色体ＤＮＡ的末端 ,由串联重复的ＤＮＡ序列与端粒结合蛋白组成的特殊结构。由于端粒能保证线性染色体ＤＮＡ完全复制 ,并防止染色体端—端融合 ,重组与降解 ,故它对稳定染色体的结构并保持基因完整有重要作用。在含有端粒酶的细胞中 ,由端粒酶维持端粒的长度。单细胞真核生物因含有端粒酶使其端粒的长度保持在一定范围内 ,且不受培养条件与培养时间的影响 ,这些细胞具有调节端粒酶活性的机制以保持端粒的长度。在正常的人体中 ,除了胚细胞、生殖细胞及骨髓造血干细胞等少数细胞外 ,其他的细胞缺乏端粒酶活性。这…     

端粒与端粒酶--人类攻克癌症的新契机

端粒,是染色体末端所特有的结构,其长度与细胞的复制及衰老有关;端粒酶,是一种催化延长端粒末端的反向转录酶。近年来的研究显示,绝大部分恶性肿瘤具有端粒酶活性表达,该酶在肿瘤的治疗和发展中起着重要作用。因此,有效地控制端粒酶活性,有可能为人类攻克癌症提供一个新的契机。     

端粒及端粒酶与肿瘤

端粒是染色体末端独特的DNA-蛋白质结构,端粒酶是能够延长端粒的特殊的反转录酶.近年来的研究发现端粒的长度和端粒酶活性的变化与细胞的衰老死亡及肿瘤发生有着密切的关系,本文就这方面的进展作一简单的介绍.     

贯叶连翘提取物和美沙酮对海洛因依赖大鼠端粒酶活性和抗氧化能力的影响

目的研究贯叶连翘提取物(Hypericum perforatum linn extract,HPLE)和美沙酮对海洛因依赖大鼠端粒酶活性和抗氧化能力的影响.方法将24只健康大鼠随机分成正常组、模型组、HPLE+美沙酮处理组、美沙酮处理组.除正常组外,其余三组动物均按递增法采用皮下注射海洛因建立海洛因依赖大鼠模型,造模后药物处理30 d,然后分别用药物进行治疗.采用PCR-ELISA检测大鼠端粒酶活性,分光光度法检测大鼠超氧化物歧化酶(superoxide dismutase,SOD)、过氧化氢酶(catalase,CAT)活性及丙二醛(malondialdehyde,MDA)含量.结果与正常组相比,模型组大鼠心、肝和脑端粒酶活性及SOD、CAT活性显著降低,MDA含量显著升高;与模型组相比,HPLE+美沙酮组和美沙酮组大鼠心、肝和脑端粒酶活性及SOD、CAT活性明显升高,MDA含量明显降低,其中HPLE和美沙酮的联合用药效果显著优于美沙酮治疗组.结论HPLE和美沙酮联合治疗海洛因造成的自由基损害疗效优于单一用药.     

端粒酶和癌症的关系

端粒酶是由RNA和蛋白质亚基组成的一种逆转录酶,具有维持和控制端粒长度的功能,其活性变化与细胞癌变有密切关系,在癌细胞的恶性转化过程中,端粒酶的活化是一个重要步骤.抑制端粒酶活性在肿瘤治疗方面有着广阔的前景.     

端粒与端粒酶

端粒是染色体末端ＤＮＡ重复序列,与各种结合蛋白一起保持染色体末端的稳定。端粒普遍存在于真核细胞中,其长度因种而异。有端粒酶时,其长度处在伸缩的动态平衡中;在没有端粒酶的细胞中,端粒长度随细胞分裂次数增加而减少。这种缩短是否与细胞寿命以及凋亡肯关,已成为目前研究的热点。端粒酶的作用是合成新的端粒和维持现有的端粒。端粒酶的作用不是独立的,很可能是与其它相关蛋白质相互作用以完成各种功能。已发现大多数肿瘤     

细胞和遗传变异进化热点例析

1.细胞衰老阅读、分析下列材料,并结合你所学的知识回答问题:细胞衰老是一种正常的生命现象。科学家提出的"端粒学说"阐述了细胞衰老的某些可能的机制。端粒是染色体末端的一种特殊结构.其DNA末端含有由简单的串联重复序列(如下图中的—TTAGGG—)组成的单链突出段.     

端粒、端粒酶与造血干细胞

端粒是由染色体末端的DN A重复序列组成的,其上有蛋白结合。可保护染色体免受伤害,与细胞周期过程中DN A末端片断的流失、细胞凋亡有关。端粒酶由hTERC和hTERT组成,可以维持端粒的稳定。造血干细胞有一定的端粒酶活性,目前已研究出多种因素影响其表达。端粒酶相关基因修饰干细胞可以达到建立永生化细胞系等目的,亦有很好的应用前景。最近,在研究端粒酶在人类造血系统的作用时,人们把目光集中到一种罕见的遗传病DCK上。治疗这种疾病可能需要进一步的研究来揭示hTERT的内在基因和外来因素的两种调节之间的关系。     

端粒与端粒酶的生物学特性

端粒的长度决定了细胞的寿命，端粒酶的活性影响着端粒的长度，本文对端粒，端粒酶的生物学特性进行了阐述。     

DNA-damage response network at the crossroads of cell-cycle checkpoints,cellular senescence and apoptosis

Tissue homeostasis requires a carefully-orchestrated balance between cell proliferation, cellular senescence and cell death. Cells proliferate through a cell cycle that is tightly regulated by cyclin-dependent kinase activities. Cellular senescence is a safeguard program limiting the proliferative competence of cells in living organisms. Apoptosis eliminates unwanted cells by the coordinated activity of gene products that regulate and effect cell death. The intimate link between the cell cycle, cellular senescence, apoptosis regulation, cancer development and tumor responses to cancer treatment has become eminently apparent. Extensive research on tumor suppressor genes, oncogenes, the cell cycle and apoptosis regulatory genes has revealed how the DNA damage-sensing and -signaling pathways, referred to as the DNA-damage response network, are tied to cell proliferation, cell-cycle arrest, cellular senescence and apoptosis. DNA-damage responses are complex, involving ＂sensor＂ proteins that sense the damage, and transmit signals to ＂transducer＂ proteins, which, in turn, convey the signals to numerous ＂effector＂ proteins implicated in specific cellular pathways, including DNA repair mechanisms, cell-cycle checkpoints, cellular senescence and apoptosis. The Bcl-2 family of proteins stands among ＂the mos＂t crucial regula＂tors of apop＂tosis and performs vi＂tal func＂tions in deciding whether a cell will live or die after cancer chemotherapy and irradiation. In addition, several studies have now revealed that members of the Bcl-2 family also interface with the cell cycle, DNA repair/recombination and cellular senescence, effects that are generally distinct from their function in apoptosis. In this review, we report progress in understanding the molecular networks that regulate cell-cycle checkpoints, cellular senescence and apoptosis after DNA damage, and discuss the influence of some Bcl-2 family members on cell-cycle checkpoint regulation.     

端粒、端粒酶与肿瘤

对近年来端粒、端粒酶的结构与功能、端粒酶与肿瘤的关系进行了综述。     

Proteins induced by telomere dysfunction are associated with human IgA nephropathy

Aging is one of the contributing risk factors for kidney diseases. Accumulating evidence prompts the view that telomere length in kidney tissue cells is an indicator for organismal aging. Previously identified aging markers (cathelin-related antimicrobial peptide (CRAMP), stathmin, elongation factor-1α (EF-1α), and chitinase) were associated not only with telomere driven aging in mice but also with human aging and chronic diseases. This study focuses on the relationship between these biomarkers and IgA nephropathy (IgAN) progression in the Chinese population. For 260 individuals, the four markers are determined in blind datasets using direct enzyme-linked immunosorbent assay (ELISA) and immunofluorescence staining. The expression levels of CRAMP and chitinase increased in blood plasma, urine, and kidney tissues during human IgAN progression. And for the other nephropathy, such as systemic lupus erythematosus (SLE), diabetic nephropathy (DN), and focal segmental glomerulosclerosis (FSGS), there is no protein upregulation with telomere shortening. Moreover, a combination of CRAMP and chitinase can distinguish patients with IgAN from healthy individuals with 88.2%/92.5% (plasma) and 74.3%/84.2% (urine) sensitivity/specificity. These data provide the experimental evidence that telomere shortening and related inflammatory proteins are associated with human IgAN, and it could be a new direction for the disease progression study.     

Telomerase RNA and telomerase activity in trophoblastic tumors

To gain better understanding of telomerase’s possible role in the carcinogenesis of gestational trophoblastic tumors, the authors conducted RT-PCR amplification-based analysis and carried out telomeric repeat amplification to determine the levels of the human telomerase RNA (hTR) and that of telomerase enzymatic activity itself in 43 normal human placental tissues, 35 gestational trophoblastic tumor tissues and three choriocarcinoma cell lines. hTR was expressed in malignant gestational trophoblastic tumor tissues as well as choriocarcinoma cell lines. The results showed that hTR of early placenta villi and a part of hydatidiform mole were positive. But relatively low levels of the hTR could be found in placental tissues. Telomerase enzymatic activity was strongly positive in 32 of the 35 (91.4%) gestational trophoblastic tumor tissues and all the three choriocarcinoma cell lines. The enzymatic activity of telomerase itself was detectable at relatively low lelves in 14 of the 21 (66.7%) early placental villi, only three of the 22 (13.6%) term placenta were weakly positive. These results suggest that telomerase activity may be correlated with the development of trophoblastic tumors, and so, may be a useful diagnostic marker for detecting the existence of malignant trophoblastic cells. Project (39670753) supported by NSFC     

Immortalization of human umbilical vein endothelial cells with telomerase reverse transcriptase and simian virus 40 large T antigen

Objective: To establish normally conditionally-immortalized human umbilical vein endothelial cells (HUVECs) by ectopic expression of the human telomerase catalytic enzyme (hTERT) and simian virus 40 large T (SV40 LT) antigen. Methods: Primary HUVECs were transfected with recombinant retrovirus containing hTERT or SV40 LT respectively. Subsequently drug resistant cell clones were screened and expanded for further studies. Endothelial cell biomarkers were confirmed by examination. Results: The morphological phenotype of the transfected cells was similar to the non-transfected cells. Von Willebrand factor, hTERT and SV40 LT could be detected in transfected HUVECs. Moreover, higher telomerase activity in transfected cells was maintained for over 50 population doublings compared with only low level of endogenous telomerase transiently at early population doublings in primary HUVECs. When exposed to TNF-α(tumor necrosis factor-α), the expression of E-selectin in transfected cells was significantly up-regulated, but no alteration of endothelial lipase was found. Conclusion: Ectopic coexpression of hTERT and SV40 LT can effectively immortalize HUVECs without tumorigenicity in vitro. Immortalized HUVECs may be an ideal target of further molecular function studies.