telomerase

摘要： Most people associate the enzyme telomerase with its role in maintaining telomeres,which is its best-known canonical role.For this important function,two main components are required:the protein telomerase reve rse transcriptase(TERT)and the telomerase RNA component.In addition,over the last decades,an ever-growing number of othe r,non-telomeric,non-canonical functions for the telomerase protein TERT has been established.These reach from tumor promotion to decreasing oxidative stress and apoptosis as well as activating autophagy.These functions are more and more recognized as being important in many tissues and physiological as well as pathological conditions.The role of telomerase in brain development and neuronal cells has been investigated for more than 20 years.However,the non-telomeric role in non-dividing neurons of the brain for telomerase and the TERT-protein has only recently been highlighted by extensive research.Moreover,these developments promoted the suggestion of a beneficial and protective role of TERT against neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease.This review summarizes the most important findings in the field of telomerase in neuro ns and gives an outlook onto possible therapeutic applications of boosting telomerase/TERT levels with telomerase activators to prevent or ameliorate various neurodegene rative diseases.

摘要： Telomerase is a nucleoprotein that contains reverse transcriptase activity. It is reversely transcribed into DNA at the end of its chromosome using its own RNA as a template to ensure the length and stability of telomeres. Its physiological function is closely related to the life process of cells. In recent years, the research on telomeres and telomerase has become a new hotspot, people have a more in-depth research and scientific understanding of their structures and functions, and scientists have also attached great importance to the research progress of telomerase increasingly. Researchers in parasite-related research have successively discovered a large number of telomere and telomerase sequences in a variety of different parasites. These achievements have greatly facilitated the scientific research of diseases caused by parasitic infections, providing a solid research basis for the preparation of new drugs, while enriching the treatment protocols of parasitic diseases, and opening new worlds for the prevention of certain diseases and epidemic transmission. This paper reviews the current research progress of telomerase.

摘要： Telomerase is an enzyme that maintains the length of telomeres at the ends of chromosomes.Telomeres are protective caps at the ends of chromosomes that keep genetic information intact,enable cells to multiply and provide insight into some of the mysteries of ageing and cancer.Telomerase activity affects ageing and cancer development in humans by preventing telomeres from becoming too short,which can lead to cellular senescence and death.When telomerase is suppressed,cancer cells die,and telomerase inhibitors can be used to kill human breast and prostate cancer cells grown in the laboratory.Studies have also found an association between shorter telomeres,a decreased overall lifespan,and an increased risk of cardiovascular disease and infectious illness.Despite research linking telomere shortening to the ageing process,additional research is needed to fully understand the role of telomerase in the ageing process,including whether or not it is the cause of these changes.Other variables,such as oxidative stress,glycation,and inflammation,also contribute to the ageing process and may explain the remaining 33 percent of the variance in the probability of passing away.The authors of this paper discuss the current understanding of telomerase enzyme activity and its effects on ageing and cancer,as well as the implications of telomerase research and the potential for developing innovative drugs and gene therapies.

摘要： Background: hTERT is a key player in telomere biology and its activity is directly related to cell senescence and development of many health-related problems including cancer. Although previous studies investigated this association, the results greatly vary among populations. This study aimed to investigate the association of hTERT gene SNPs and the risk of breast cancer (BC) in Egyptian females and their impact on telomere length (TL). Methods: 218 BC patients and 178 age-matched healthy females were genotyped for hTERT variants rs2736098G > A, rs2735940C > T using PCR-RFLP and for MNS16A tandem repeat using PCR to determine their association with breast cancer risk. Telomere length was measured using qPCR. Results: hTERT rs2736098G > A results indicated that both AG and GG genotypes and G allele were associated with an increased risk of BC. The rs2735940 TT genotype was significantly associated with BC risk, however, the MNS16A tandem repeat region polymorphism didn’t show any correlation with the risk of developing BC. TL showed a significant reduction in BC patients with age 40 years compared with controls. However, it didn’t show a significant difference above the age of 40 years. Conclusions: hTERT rs2736098 and rs27365940, not MNS16A may be associated with an increased risk of developing BC in Egyptian females. Also, telomere length can be a promising screening marker of BC especially in young population.

摘要： Telomere, the nucleoprotein structure at the end of eukaryotic linear chromosomes is indispensable for maintaining the genome stability. Telomeric DNA loss is apparent with each cell division, which marks an endpoint to the indefinite replication of the cell by causing replicative senescence that may lead to the programmed cell death. The loss of telomere is normal in cell division and as such after 20 - 40 divisions, telomere becomes too short to facilitate the capping function. Telomere uncapping or chromosomal free end causes a potential threat to the genomic stability and thus leads to the accumulation of chromosomal abnormalities that have been known to play a role in aging and cancer. Telomerase, the ribonucleoprotein complex, and its accessory proteins are required to maintain the telomere sequence. Telomerase plays a key role in maintaining the length of telomere by adding G-rich repeat sequences. Its activity has been found to be quite high in the gametes, stem cells and most importantly tumor cells. Almost 85% of tumor cells compensate for telomere loss aided by telomerase-associated protein complex and shelter in complex or telosome. However, 5% - 10% of the cells undergo telomerase-independent mechanism. This review presents the molecular view of the telomere and telomerase along with its associated complex structures. It also discusses its contrasting role in causing cellular senescence and promoting tumorigenesis.

摘要： Aging is a decelerating unidirectional process of life. Shortening of telomeric DNA, the (TTAGGG)n hexanucleotide repeats, which form the caps at the chromosome ends, is implicated to determine the aging process, and more importantly the healthy lifespan itself. Telomerase, a ribonucleoprotein having reverse transcriptase activity, arrests telomere loss through addition of the TTAGGG repeats de novo, to the ends of the chromosome. The telomere/telomerase maintenance is an inevitable necessity to delay aging and for a healthy lifespan. Here, we report the potential of full-spectrum, high concentration Ashwagandha (Withania somnifera), an Ayurvedic medicinal herb, root extract to increase telomerase activity. HeLa cells, when treated with various concentrations of Ashwagandha root extract, showed an increase in telomerase activity measured with the established Telomerase Rapid Amplification Protocol (TRAP) assay. Ashwagandha root extract increased telomerase activity with highest enhancement of ~45% at 10 - 50 μg concentration. Thus, Ashwagandha root extract has the anti-aging inducing potential.

摘要： AIM To analyse the long-term prognostic impact of circulating tumour cells(CTCs) in gastric cancer patients who underwent surgery. METHODS A 7.5-m L peripheral vein blood sample was obtained from each patient with treatment-negative gastric adenocarcinoma before surgery. OBP-401, a telomerasespecific, replication-selective, oncolytic adenoviral agent carrying the green fluorescent protein gene, was used to label CTCs. Correlations between the number of CTCs and clinical end points were evaluated. RESULTS The median follow-up period of the surviving patients with gastric cancer was 60 mo. The CTC number tended to increase concomitantly with disease progression. The overall survival of patients with more than five CTCs in 7.5-m L of peripheral blood was lower than that of patients with five or less CTCs, although the difference was not significant(P = 0.183). A significant difference in relapse-free survival was found between patients with more than five and those with five or less CTCs(P = 0.034).CONCLUSION A lower number of CTCs was correlated with higher relapse-free survival rates in patients. Detection of CTCs using OBP-401 may be useful for predicting prognosis in gastric cancer.

摘要： AIM: To investigate the functional consequences of rs2736100 polymorphism in telomere length and examine its link to gastric cancer risk.METHODS: Telomere length and human telomerase reverse transcriptase(h TERT) m RNA expression were measured in 35 gastric cancer tissues and 5 cell lines and correlated to rs2736100 polymorphism. The relationship between rs2736100 polymorphism and the risk of gastric cancer were examined in 243 gastric cancer patients and 246 healthy individuals.RESULTS: The rs2736100 A allele carrier is closely associated with reduced h TERT m RNA expression and shortened telomere length in gastric cancer tissue and cell lines. When gastric cancers were stratified by histological subtype,telomere length and h TERT m RNA levels were significantly increased in those with the C/C genotype in intestinal-type gastric cancer,but not in diffuse-type gastric cancer. Interestingly,there was no significant difference in the genotype and allele frequencies of the rs2736100 polymorphism between the patients with gastric cancer and healthy controls.CONCLUSION: The rs2736100 polymorphism of the h TERT gene is involved in the regulation of h TERT expression and telomere length,but not in the risk of gastric cancer.

摘要： AIM: To determine the mutation status of human telomerase reverse transcriptase gene(TERT) promoter region in hepatocellular carcinoma(HCC) from different geographical regions.METHODS: We analyzed the genomic DNA sequences of 59 HCC samples comprising 15 cell lines and 44 primary tumors,collected from patients living in Asia,Europe and Africa.We amplified a 474 bp DNA fragment of the promoter region of TERT gene including the 1295228 and 1295250 sequence of chromosome 5 by using PCR.Amplicons were then sequenced by Sanger technique and the sequence data were analyzed with by using DNADynamo software in comparison with wild type TERT gene sequence as a reference.RESULTS: The TERT mutations were found highly frequent in HCC.Eight of the fifteen tested cell lines displayed C228 T mutation,and one had C250 T mutation with a mutation frequency up to 60%.All of the mutations were heterozygous and mutually exclusive.Ten out of forty-four tumors displayed C228 T mutation,and additional five tumors had C250 T mutation providing evidence for mutation frequency of 34% in primary tumors.Considering the geographic origins of HCC tumors tested,TERT promoter mutation frequencies were higher in African(53%),when compared to non-African(24%) tumors(P = 0.056).There was also a weak inverse correlation between TERT promoter mutations and murine double minute 2 single nucleotide polymorphism 309 TG polymorphism(P = 0.058).Mutation frequency was nearly two times higher in established HCC celllines(60%) compared to the primary tumors(34%).CONCLUSION: TERT promoter is one of most frequent mutational targets in liver cancer,and hepatocellular carcinogenesis is highly associated with the loss of telomere-dependent cellular senescence control.

摘要： Repair and regeneration of bone requires mesenchymal stem cells that by self-renewal,are able to generate a critical mass of cells with the ability to differentiate into osteoblasts that can produce bone protein matrix(osteoid)and enable its mineralization.The number of human mesenchymal stem cells(hMSCs)diminishes with age and ex vivo replication of hMSCs has limited potential.While propagating hMSCs under hypoxic conditions may maintain their ability to self-renew,the strategy of using human telomerase reverse transcriptase(hTERT)to allow for hMSCs to prolong their replicative lifespan is an attractive means of ensuring a critical mass of cells with the potential to differentiate into various mesodermal structural tissues including bone.However,this strategy must be tempered by the oncogenic potential of TERT-transformed cells,or their ability to enhance already established cancers,the unknown differentiating potential of high population doubling hMSCs and the source of hMSCs(e.g.,bone marrow,adipose-derived,muscle-derived,umbilical cord blood,etc.)that may provide peculiarities to self-renewal,differentiation,and physiologic function that may differ from non-transformed native cells.Tissue engineering approaches to use hMSCs to repair bone defects utilize the growth of hMSCs on three-dimensional scaffolds that can either be a base on which hMSCs can attach and grow or as a means of sequestering growth factors to assist in the chemoattraction and differentiation of native hMSCs.The use of whole native extracellular matrix(ECM)produced by hMSCs,rather than individual ECM components,appear to be advantageous in not only being utilized as a three-dimensional attachment base but also in appropriate orientation of cells and their differentiation through the growth factors that native ECM harbor or in simulating growth factor motifs.The origin of native ECM,whether from hMSCs from young or old individuals is a critical factor in"rejuvenating"hMSCs from older individuals grown on ECM from younger individuals.