共查询到19条相似文献，搜索用时 203 毫秒
1.
端粒是真核生物染色体末端的一种特殊的DNA-蛋白质结构,对染色体的稳定性有重要作用.端粒酶是一种由蛋白质和RNA组成的核糖核蛋白复合物.端粒酶活性的测定方法主要是以TRAP为基础的改良法.近来,越来越多的研究结果表明在多数肿瘤、细胞癌变和衰老过程中都可检测到很高的端粒酶活性和端粒长度缩短.但同时也有许多不依赖端粒酶的端粒维持和细胞永生.目前,有关以端粒酶为靶位点的药物设计的研究已广泛开展. 相似文献
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端粒酶与体细胞重编程是当今生物界最热门的研究领域之一。研究端粒酶能揭示生物体胚胎早期发育、衰老和癌症发生的机制;细胞重编程则有望从根本上解决体细胞克隆技术问题,从而开启生命再造新时代。文章通过对端粒酶与体细胞重编程及二者互作机制的最新研究进展进行详细阐述,发现细胞重编程面临的主要问题是效率低下,其根本原因是对其作用机制尚未完全了解;而最新研究证实,生殖细胞的端粒酶活性发生时序性变化可能在胚胎发育及细胞重编程过程中发挥重要调控作用。因此,揭示细胞重编程机制是今后研究工作的重心,尤其是揭示端粒酶在胚胎发育过程的分子调控机理及端粒酶调控细胞重编程可能开启的信号通路,对提高细胞重编程效率,推进克隆动物的生产实践并开启生命再造,以及为治疗癌症等人类重大疾病具有重要意义。 相似文献
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端粒酶(telom erase)是一种蛋白质与RNA组成的核糖核蛋白,是目前发现的唯一能够延长端粒的一种RNA依赖性DNA聚合酶。在DNA复制过程中丢失的端粒可以被有活性的端粒酶修复回来。哺乳动物端粒酶在发育中受调控,端粒的重编程可能是由于早期胚胎不同时期的端粒酶活性而造成的,因此,研究端粒和端粒酶重编程将为哺乳动物体细胞克隆技术奠定重要的理论基础。本文综述了端粒和端粒酶的结构和功能,及其与哺乳动物体细胞克隆早期胚胎发育的关系,并在此基础上探讨了端粒酶在体细胞克隆动物胚胎发育中的重要作用。 相似文献
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[目的]研究鹿茸生长期端粒酶的表达,为揭示鹿茸生长发育的调控机制提供了新思路。[方法]在鹿茸快速生长阶段,采用改进的TRAP（端粒重复序列扩增技术）法检测鹿茸顶端增殖区的间充质层、前软骨层和软骨层细胞及下端成熟区的端粒酶活性。同时,采用RT-PCR的方法检测各组织细胞中端粒酶催化亚基（TERT）mRNA的表达水平。[结果]在顶端增生区各组织细胞中均检测到了不同程度的端粒酶活性,间质细胞、前软骨细胞和软骨细胞中的相对端粒酶活力分别为91.2、46.4和13.7,而在成熟区组织中则检测不到端粒酶活性。RT-PCR法检测的各组织细胞中TERTmRNA的表达水平与端粒酶活性检测结果一致。[结论]在鹿茸快速生长阶段,其增殖区表达端粒酶,并且端粒酶活性随组织层细胞的分化程度的增高而逐渐降低,说明端粒酶可能在鹿茸的生长过程中起重要的调控作用。 相似文献
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顺铂对鼻咽癌细胞株端粒酶活性和凋亡的影响 总被引：1，自引：1，他引：1
目的：研究抗癌药顺铂对5株鼻咽癌细胞端粒酶活性和凋亡的影响．以探讨端粒酶活性水平与鼻咽癌的关系及顺铂诱导鼻咽癌细胞凋亡的可能机制，为端粒酶可能成为一种很好的鼻咽癌治疗靶点提供实验依据。方法：用TRAP—ELISA的方法定量检测5株鼻咽癌细胞在顺铂处理前后的端粒酶活性水平，观察细胞形态及生长状态．以流式细胞仪分析细胞周期的改变并检测凋亡。结果：5株鼻咽癌细胞端粒酶均呈阳性，其中LTRs—LMP细胞株端粒酶活性水平最高，高分化细胞株CNE—1端粒酶活性水平低于低分化细胞株CNE—2Z、HNE—2。经顺铂处理后5株鼻咽癌细胞端粒酶活性明显受抑制、细胞形态发生明显改变，出现细胞凋亡。结论：端粒酶的活化与鼻咽癌密切相关。临床常用化疗药物顺铂可能是通过在S期抑制端粒酶活性并诱导鼻咽癌细胞凋亡而发挥杭癌作用的。因此我们认为端粒酶可以作为鼻咽癌的一个治疗靶点。 相似文献
6.
为了解延边黄牛体细胞克隆早期胚胎发育过程中端粒酶活性的变化规律,采用实时荧光定量PCR法检测体细胞克隆早期胚胎及卵母细胞端粒酶活性.研究结果表明,端粒酶活性在未成熟卵母细胞相对水平较高,2-细胞至16-细胞胚胎的端粒酶活性总体水平相对较低(P<0.05),桑椹胚的端粒酶活性总体水平显著升高(P<0.05),在囊胚阶段达到最高. 相似文献
7.
端粒(telomere)位于真核细胞染色体末端,是末端DNA和蛋白质的复合体,随细胞的分裂而缩短,同时,细胞衰老也就开始.端粒酶(telomerase)是一种核糖核蛋白(RNP)DNA聚合酶,直接参与端粒区DNA的合成.通过激活端粒酶,可以延长端粒区,以抵消由于细胞分裂而导致的DNA片段的缩短,间接地延缓了细胞衰老现象.本文介绍了端粒-端粒酶假说与细胞衰老的关系.同时,也简述了端粒在动物克隆技术方面的研究进展. 相似文献
8.
目的观察漆树黄酮对人肝癌细胞系HepG2端粒酶活性及NF-κBp65表达的影响。方法端粒酶重复序列扩增-酶联免疫吸附法（TRAP-ELISA）检测不同浓度漆树黄酮对HepG2细胞端粒酶活性的影响,RT-PCR法检测端粒酶逆转录酶（hTERT）mRNA表达,Western blot检测NF-κBp65蛋白表达。结果漆树黄酮对端粒酶活性具有抑制作用。漆树黄酮组hTERT mRNA和NF-κBp65蛋白表达降低,并且与端粒酶活性下调存在相关性。结论漆树黄酮可能通过下调NF-κBp65蛋白表达而抑制HepG2细胞hTERTmRNA转录,导致端粒酶活性降低。 相似文献
9.
端粒酶是一种能够以自身的RNA组分为模板在染色体末端添加端粒重复序列的核酸蛋白复合体酶，主要由端粒酶RNA组分（TERC）与端粒酶逆转录酶组分（TERT）构成。通过对成年牛组织中端粒酶的这两种组分的表达情况及端粒酶活性状态进行检测，探讨牛端粒酶组分的组织特异性表达以及与端粒酶活性之间的关系。应用RT-PCR检测了成年牛的心脏、肾脏、肝脏及睾丸中TERC和TERT基因的mRNA表达情况，利用TRAP银染法检测各组织中的端粒酶活性状态。结果表明砸RC基因在这4种组织中均有表达，但转录水平在各组织之间有差异；TERT基因仅在睾丸中表达，在其他3种组织中均没有表达，端粒酶活性同样只在睾丸中检测到。由此可见牛端粒酶活性在体细胞中普遍受到抑制，仅在生殖腺中具有活性。端粒酶两种组分的转录是相互独立的，逆转录酶TERT组分是端粒酶活性的关键成分。 相似文献
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Senescence induced by altered telomere state, not telomere loss 总被引：1，自引：0，他引：1
Primary human cells in culture invariably stop dividing and enter a state of growth arrest called replicative senescence. This transition is induced by programmed telomere shortening, but the underlying mechanisms are unclear. Here, we report that overexpression of TRF2, a telomeric DNA binding protein, increased the rate of telomere shortening in primary cells without accelerating senescence. TRF2 reduced the senescence setpoint, defined as telomere length at senescence, from 7 to 4 kilobases. TRF2 protected critically short telomeres from fusion and repressed chromosome-end fusions in presenescent cultures, which explains the ability of TRF2 to delay senescence. Thus, replicative senescence is induced by a change in the protected status of shortened telomeres rather than by a complete loss of telomeric DNA. 相似文献
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Cells from Werner syndrome patients are characterized by slow growth rates, premature senescence, accelerated telomere shortening rates, and genome instability. The syndrome is caused by the loss of the RecQ helicase WRN, but the underlying molecular mechanism is unclear. Here we report that cells lacking WRN exhibit deletion of telomeres from single sister chromatids. Only telomeres replicated by lagging strand synthesis were affected, and prevention of loss of individual telomeres was dependent on the helicase activity of WRN. Telomere loss could be counteracted by telomerase activity. We propose that WRN is necessary for efficient replication of G-rich telomeric DNA, preventing telomere dysfunction and consequent genomic instability. 相似文献
14.
A key process in organ homeostasis is the mobilization of stem cells out of their niches. We show through analysis of mouse models that telomere length, as well as the catalytic component of telomerase, Tert, are critical determinants in the mobilization of epidermal stem cells. Telomere shortening inhibited mobilization of stem cells out of their niche, impaired hair growth, and resulted in suppression of stem cell proliferative capacity in vitro. In contrast, Tert overexpression in the absence of changes in telomere length promoted stem cell mobilization, hair growth, and stem cell proliferation in vitro. The effects of telomeres and telomerase on stem cell biology anticipate their role in cancer and aging. 相似文献
15.
The aging of organisms is characterized by a gradual functional decline of all organ systems. Mammalian somatic cells in culture display a limited proliferative life span, at the end of which they undergo an irreversible cell cycle arrest known as replicative senescence. Whether cellular senescence contributes to organismal aging has been controversial. We investigated telomere dysfunction, a recently discovered biomarker of cellular senescence, and found that the number of senescent fibroblasts increases exponentially in the skin of aging baboons, reaching >15% of all cells in very old individuals. In addition, the same cells contain activated ataxia-telangiectasia mutated kinase and heterochromatinized nuclei, confirming their senescent status. 相似文献
16.
Rudolph KL Chang S Millard M Schreiber-Agus N DePinho RA 《Science (New York, N.Y.)》2000,287(5456):1253-1258
Accelerated telomere loss has been proposed to be a factor leading to end-stage organ failure in chronic diseases of high cellular turnover such as liver cirrhosis. To test this hypothesis directly, telomerase-deficient mice, null for the essential telomerase RNA (mTR) gene, were subjected to genetic, surgical, and chemical ablation of the liver. Telomere dysfunction was associated with defects in liver regeneration and accelerated the development of liver cirrhosis in response to chronic liver injury. Adenoviral delivery of mTR into the livers of mTR(-/-) mice with short dysfunctional telomeres restored telomerase activity and telomere function, alleviated cirrhotic pathology, and improved liver function. These studies indicate that telomere dysfunction contributes to chronic diseases of continual cellular loss-replacement and encourage the evaluation of "telomerase therapy" for such diseases. 相似文献
17.
Mutations in the yeast Saccharomyces cerevisiae PIF1 gene, which encodes a 5'-to-3' DNA helicase, cause telomere lengthening and a large increase in the formation rate of new telomeres. Here, we show that Pif1p acts by inhibiting telomerase rather than telomere-telomere recombination, and this inhibition requires the helicase activity of Pif1p. Overexpression of enzymatically active Pif1p causes telomere shortening. Thus, Pif1p is a catalytic inhibitor of telomerase-mediated telomere lengthening. Because Pif1p is associated with telomeric DNA in vivo, its effects on telomeres are likely direct. Pif1p-like helicases are found in diverse organisms, including humans. We propose that Pif1p-mediated inhibition of telomerase promotes genetic stability by suppressing telomerase-mediated healing of double-strand breaks. 相似文献
18.
Although broken chromosomes can induce apoptosis, natural chromosome ends (telomeres) do not trigger this response. It is shown that this suppression of apoptosis involves the telomeric-repeat binding factor 2 (TRF2). Inhibition of TRF2 resulted in apoptosis in a subset of mammalian cell types. The response was mediated by p53 and the ATM (ataxia telangiectasia mutated) kinase, consistent with activation of a DNA damage checkpoint. Apoptosis was not due to rupture of dicentric chromosomes formed by end-to-end fusion, indicating that telomeres lacking TRF2 directly signal apoptosis, possibly because they resemble damaged DNA. Thus, in some cells, telomere shortening may signal cell death rather than senescence. 相似文献
19.
Replicative senescence: the human fibroblast comes of age 总被引：59，自引：0，他引：59
S Goldstein 《Science (New York, N.Y.)》1990,249(4973):1129-1133