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1.
端粒酶与细胞永生化   总被引:2,自引:0,他引:2  
端粒是真核细胞染色体末端的一种特殊结构,由端粒DNA和端粒蛋白质组成。正常动物细胞DNA的端粒随着细胞分裂而缩短,当缩短到一定长度时细胞将停止增殖并死亡。端粒酶可以从端粒DNA 3′OH末端延伸端粒或合成新的端粒。本文主要介绍了端粒酶的结构和功能以及在细胞永生化中的应用。  相似文献   

2.
细胞衰老机制是细胞生物学研究的一个重要课题。随着端粒及端粒酶与细胞衰老和年龄增长关系的揭示,端粒长度的缩短已经成为细胞衰老和年龄增长的生物学标志之一。作者首先介绍了端粒和端粒酶的结构、功能,进而分析其与细胞衰老、年龄增长的关系,并对端粒和端粒酶在年龄推断中的应用研究加以综述。  相似文献   

3.
真核细胞的衰老及凋亡与端粒DNA序列长度的缩短有关。端粒相关蛋白则可能通过调节端粒酶或其他相关因子的行为对端粒长度进行调控。目前端粒的长度可作为细胞衰老的生物学指标之一。文中综述了端粒的结构、功能、相关蛋白及其与细胞衰老的关系。  相似文献   

4.
端粒酶是真核生物细胞染色体末端富含G的简单重复结构。在生理状况下,随着细胞分裂次数增加,端粒在复制分裂过程中将逐渐丢失碱基,从而致使端粒逐渐缩短。当端粒缩短至一定长度时细胞将进人生长停止衰老死亡阶段,即出现细胞的凋亡。最近几年来,人们研究发现一种端粒酶能够逆转录合成端粒DNA,并添加到端粒从而达到防止端粒缩短,维持端粒的长度,进而保持染色体的稳定性。由于大多数生物体细胞生理状态下,  相似文献   

5.
端粒和端粒酶的研究进展   总被引:7,自引:4,他引:3  
端粒和端粒酶是现代生物学研究的热点,端粒封闭了染色体的末端并维持了染色体的稳定性,端粒的缺失会引起染色体融合并导致细胞的衰老及死亡.端粒酶的活化可延长染色体末端DNA,维持基因组的稳定.并且端粒酶活性的异常表达又会引起细胞永生化或转化成癌细胞.因此端粒和端粒酶的结构和功能的研究对于治疗肿瘤和控制细胞寿命有着极其重要的意义.文章综述了端粒和端粒酶的结构和功能,及其与细胞老化的关系,并在此基础之上展望了端粒酶在抑制肿瘤、抗衰老等方面的应用.  相似文献   

6.
端粒和端粒酶与衰老关系的研究进展   总被引:6,自引:0,他引:6  
端粒是存在于线性染色体末端的一段特殊的DNA-蛋白质复合物,由于末端不能复制,正常体细胞随着细胞分裂的进行而逐渐丢失端粒序列,导致细胞老化和死亡。端粒酶是维持端粒长度的一种特殊的DNA聚合酶,在细胞的增殖、衰老及永生中起重要作用。本文就端粒和端粒酶及其与衰老的作一综述。  相似文献   

7.
端粒、端粒酶与动物衰老相关性的研究   总被引:1,自引:0,他引:1  
端粒和端粒酶是现代生物学研究的热点, 端粒封闭染色体的末端并维持染色体的稳定性, 端粒的缺失会引起染色体融合并导致细胞的衰老及死亡。端粒酶的活化可延长染色体末端DNA , 维持基因组的稳定。并且端粒酶活性的异常表达又会引起细胞永生化或转化成癌细胞。因此,端粒和端粒酶的结构和功能的研究对于治疗肿瘤和控制细胞寿命有着极其重要的意义。作者综述端粒和端粒酶的结构和功能, 及其基因和调控机理, 并在此基础之上展望了端粒酶在抑制肿瘤、抗衰老等方面的应用。  相似文献   

8.
端粒位于真核染色体末端,是稳定染色体末端的重要元件。端粒酶(TER)是一种特殊的细胞核蛋白(RNP)反转录酶(RT),其核心酶包括蛋白亚基和RNA元件。在DNA复制过程中的端粒丢失可以被有活性的端粒酶补偿回来。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,研究胚胎发育早期端粒和端粒酶重编程是非常重要的。本文对端粒和端粒酶的结构和功能,及其与哺乳动物早期胚胎发育的关系进行了综述.并在此基础上展望了端粒和端粒酶在克隆动物胚胎发育上的基础作用。  相似文献   

9.
端粒(Telomere)是真核细胞染色体末端的特异结构。由重复的端粒特异DNA和与它们特异结合的蛋白组成。在人类端粒特异DNA为5’~r丌AGGG~3’,这些重复序列的长度山种系细胞的15~20Kb到外周血白细胞的5~12Kb不等。它可以保护染色体不完全复制、防止DNA重组、被核酸酶降解,以及在复制过程中末端—末端融合。由于末断复制问题的存  相似文献   

10.
植物衰老和种子劣变机理的研究一直是农业科学领域关注的热点。植物衰老会对农业产生巨大的负面影响,牧草提前衰老也会导致草地生产力下降,限制草产业的发展。由于种子劣变,全球每年约有25%的种子失去活力,导致巨额的经济损失,严重影响农业的健康发展。深入揭示植物衰老特性和调控机制,不仅对于阐明植物生态适应性及种群稳定性具有重要价值,而且对于延缓衰老技术和调控措施的选择具有重要实践意义。在模式植物拟南芥研究中发现,染色体端粒与植物衰老以及种子活力密切相关。端粒是染色体末端的重复DNA序列,由端粒DNA和结合蛋白组成。端粒结合蛋白是一组与端粒DNA结合的蛋白质,主要是帮助稳定端粒结构并保护端粒免受DNA修复系统的干扰,其次还参与了基因表达、DNA复制和染色体结构调节等许多生物学过程。端粒酶由端粒酶逆转录酶(TERT)和端粒酶RNA(TER)两个亚单位组成,端粒酶逆转录酶亚基参与线粒体功能以及相关基因表达调控,通过对端粒酶新功能的探索,有助于提高植物的抗逆性,从而延缓植物的衰老进程,为提高作物产量提供一条新的途径。近年来在植物中研究发现,端粒的动态变化与植物衰老存在相关性,植物端粒内稳态的维持机制仍存...  相似文献   

11.
Telomeres are specific structures present at the end of liner chromosomes. DNA polymerase can not synthesize the end of liner DNA and, as a result, the telomeres become progressively shortened by successive cell divisions. To overcome the end replication problem, telomerase adds new telomeric sequences to the end of chromosomal DNA. The enzyme activity is undetectable in most normal human adult somatic cells, in which shortening of the telomere is thought to limit the somatic-cell life span. In contrast to normal somatic cells, many human tumors possess telomerase activity. The present study looked at whether telomerase activity might serve as a marker for canine tumors. Telomerase activity was measured using the telomeric repeat amplification protocol assay. Normal dog somatic tissues showed little or no telomerase activity, while normal testis exhibited a high level of telomerase activity. We measured telomerase activity in tumor samples from 45 dogs; 21 mammary gland tumors, 16 tumors developed in the skin and oral cavity, 7 vascular tumors and 1 Sertoli cell tumor. Greater than 95% of the tumor samples contained telomerase activity (3-924 U/2 micrograms protein). The results obtained in this study indicated that telomerase should be a useful diagnostic marker for a variety of dog tumors, and it may serve as a target for antitumor chemotherapy.  相似文献   

12.
端粒、端粒酶与肿瘤的关系及其应用   总被引:3,自引:0,他引:3  
端粒是染色体末端的特殊结构,其长度随细胞分裂而进行性缩短;端粒酶是一种核糖核蛋白酶,能够逆转录合成端粒,维持其长度,在几乎所有恶性肿瘤中能检测到端粒酶活性,它作为一种新的肿瘤标记物及抗癌靶点,日益受到重视,具有重要的生物学意义,可作为诊断指标和治疗方法的研究对象,应用于病理学中。  相似文献   

13.
端粒及其研究进展   总被引:1,自引:0,他引:1  
端粒是真核生物染色体末端的一种特殊结构,由端粒DNA和端粒相关蛋白组成,它能维持染色体的结构稳定和功能,保护其免受核酸酶降解,防止其末端融合或重排等。端粒长度的维持机制主要有ALT机制和TA机制。端粒长度的维持以及端粒酶的利用在衰老的控制中起重要作用。本文在系统论述端粒的结构、端粒的维持机制以及端粒与衰老的关系等研究进展的基础上,就当前该研究领域中存在的问题提出了个人的观点。  相似文献   

14.
Telomere shortening in normal somatic cells has been proposed as a major barrier to unlimited cellular proliferation. Telomerase is an enzyme capable of maintaining telomere length, and thus bypassing this barrier. In human beings, telomerase activity is restricted to cancer cells and cells of stem or germ cell lineages. Dogs represent a potentially useful clinical model for the development of telomerase‐based therapies because telomerase activity is also restricted to cancer cells and stem cells in this species. We examined the ability of telomestatin to inhibit telomerase activity in telomerase‐positive D17 and CMT7 canine cancer cell lines. At a concentration of 2 μM, telomestatin treatment resulted in a decrease in telomerase activity, telomere shortening, growth inhibition and apoptosis in telomerase‐positive cancer cells. These effects were not seen in telomerase‐negative skin fibroblasts or negative controls. These results confirm that telomestatin specifically inhibits telomerase activity in canine cancer cells and strengthens the usefulness of dogs as a model for testing telomerase‐based therapies.  相似文献   

15.
Background: We demonstrated previously that canine osteosarcoma (OSA) cell lines and samples from clinical patients are predominantly telomerase positive. In contrast, the majority of OSA samples from human patients appear to be telomerase negative, maintaining telomere length by an alternative lengthening of telomeres (ALT) mechanism. The purpose of the current study was to examine the telomerase status of a large number of OSA samples from dogs and determine if telomerase status can serve as a prognostic factor. Hypothesis: The majority of clinical canine OSA appendicular lesions will be telomerase positive, and telomerase positivity will negatively impact disease outcome. Animals: Sixty‐seven dogs with appendicular OSA presenting to the Colorado State University Animal Cancer Center for treatment. Methods: The Telomeric Repeat Amplification Protocol was performed on tissue samples from primary canine appendicular OSA to determine the presence of telomerase activity. Telomere restriction fragment (TRF) analysis was utilized to determine telomere length and detect ALT. Outcome data were obtained in a retrospective manner and correlated with telomerase status. Results: Seventy‐three percent of canine OSA samples were telomerase positive. Telomerase status did not have an impact on disease‐free interval or survival time. Nine of 10 telomerase‐negative samples examined were consistent with an ALT phenotype, based on TRF analysis. Conclusions and Clinical Importance: These results are consistent with the hypothesis that the majority of canine OSA are telomerase positive, suggesting that telomerase may be a valuable target for canine OSA therapy. Additionally, telomerase status does not appear to be a prognostic factor in canine OSA.  相似文献   

16.
端粒和端粒酶与肿瘤关系的研究进展   总被引:2,自引:0,他引:2  
端粒是末端染色体 ,维持染色体的稳定。端粒酶是染色体末端转移酶 ,是合成端粒DNA的酶 ,对端粒的结构起着稳定的作用。端粒、端粒酶的研究始于 2 0世纪初期 ,但直到近几年科研人员才发现他们与肿瘤有着密切的关系。在人类端粒酶的研究过程中发现端粒酶在约 85 %以上的恶性肿瘤中呈阳性 ,而动物肿瘤与端粒酶的研究还是空白。文章主要介绍端粒、端粒酶的结构功能及它们与肿瘤关系的研究进展 ,并讨论世界上首例蛋鸡 J亚群禽白血病的自然发病的病例的端粒酶 TERT表达。作者曾用辣根过氧化物酶标记的链酶卵白素进行免疫组化检测 ,结果在病鸡的心、肝、脾、肺、肾、气管、十二指肠、睾丸、骨髓、脑、胸腺、法氏囊等组织中发现 TERT表达呈阳性 ,说明在蛋鸡 J亚群禽白血病发生时端粒酶活性升高 ,提示端粒酶参与了该病的发生发展机制 ,并且该结果与人类肿瘤端粒酶的活性的研究结果相一致  相似文献   

17.
OBJECTIVE: To measure telomere length and telomerase activity in naturally occurring canine mammary gland tumors. SAMPLE POPULATION: 27 mammary gland tumor specimens obtained during resection or necropsy and 12 mammary gland tissue specimens obtained from healthy (control) dogs. PROCEDURE: Telomere length in tissue specimens was measured by use of restriction endonuclease digestion and Southern blot analysis. Telomerase activity was measured by use of a telomeric repeat amplification protocol assay. RESULTS: Telomere length in mammary gland tumors ranged from 11.0 to 21.6 kilobase pairs (kbp; mean +/- SEM, 14.5+/-0.5 kbp) but did not differ among tumor types. Telomeres in mammary gland tumors were slightly shorter than in normal tissue specimens, but telomere length could not be directly compared between groups, because mean age of dogs was significantly different between groups. Age was negatively correlated with telomere length in control dogs but was not significantly correlated with length in affected dogs. Telomerase activity was detected in 26 of 27 mammary gland tumors and in 4 of 12 normal tissue specimens. However, telomerase activity and telomere length were not correlated in tumor specimens. CONCLUSIONS AND CLINICAL RELEVANCE: Telomere length is maintained in canine mammary gland tumors regardless of the age of the affected dog. Measurement of telomere length may be a useful tool for monitoring the in vivo effects of telomerase inhibitors in dogs with tumors.  相似文献   

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