• Molecules and Cells
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• 제45권3호
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• pp.148-157
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• 2022

Hepatitis C virus (HCV) is a major cause of chronic liver disease and is highly dependent on cellular proteins for viral propagation. Using protein microarray analysis, we identified 90 cellular proteins as HCV nonstructural 5A (NS5A) interacting partners, and selected telomere length regulation protein (TEN1) for further study. TEN1 forms a heterotrimeric complex with CTC and STN1, which is essential for telomere protection and maintenance. Telomere length decreases in patients with active HCV, chronic liver disease, and hepatocellular carcinoma. However, the molecular mechanism of telomere length shortening in HCV-associated disease is largely unknown. In the present study, protein interactions between NS5A and TEN1 were confirmed by immunoprecipitation assays. Silencing of TEN1 reduced both viral RNA and protein expression levels of HCV, while ectopic expression of the siRNA-resistant TEN1 recovered the viral protein level, suggesting that TEN1 was specifically required for HCV propagation. Importantly, we found that TEN1 is re-localized from the nucleus to the cytoplasm in HCV-infected cells. These data suggest that HCV exploits TEN1 to promote viral propagation and that telomere protection is compromised in HCV-infected cells. Overall, our findings provide mechanistic insight into the telomere shortening in HCV-infected cells.

• Asian Pacific Journal of Cancer Prevention
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• 제13권2호
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• pp.443-446
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• 2012

Purpose: Telomeres play a key role in the maintenance of chromosome integrity and stability, and telomere shortening is involved in initiation and progression of malignancies. The aim of this study was to determine whether telomere length is associated with the colorectal carcinoma. Patients and methods: A total of 148 colorectal cancer (CRC) samples and corresponding adjacent non-cancerous tissues were evaluated for telomere length, P53 mutation, and cyclooxygenase-2 (COX-2) mutation detected by fluorescent immunohistochemistry. Telomere length was estimated by real-time PCR. Samples with a T/S>1.0 have an average telomere length greater than that of the standard DNA; samples with a T/S<1.0 have an average telomere length shorter than that of the standard DNA. Results: Telomeres were shorter in CRCs than in adjacent tissues, regardless of tumor stage and grade, site, or genetic alterations (P=0.004). Telomere length in CRCs also had differences with COX-2 status (P=0.004), but did not differ with P53 status (P=0.101), tumor progression (P=0.244), gender (P=0.542), and metastasis (P=0.488). There was no clear trend between T/S optimal cut-off values (<1 or > 1) and colorectal tumor progression, metastasis, gender, P53 and COX-2 status. Conclusion: These findings suggesting that telomere shortening is associated with colorectal carcinogenesis but does not differ with tumor progression, gender, and metastasis.

• Toxicological Research
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• 제19권3호
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• pp.161-172
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• 2003

Explanted mammalian cells perform a limited number of cell division in vitro and than are arrested in a state known as replicative senescence. Such cells are irreversibly blocked, mostly in the G1 phase of cell cycle, and are no longer sensitive to growth factor stimulation. Thus replicative senescence is defined as a permanent and irreversible loss of replicative potential of cells. For this characteristic, replicative senescence seems to evolve to protect mammalian organism from cancer. However, senescence also contributes to aging. It seems to decrease with age of the cell donor and, as a form of cell senescence, is thought to underlie the aging process. Extensive evidence supports the idea that progressive telomere loss contributes to the phenomenon of cell senescence. Telomeres are repetitive structures of the sequence (TTAGGG)n at the ends of linear chromosomes. It has been shown that the average length of telomere repeats in human somatic cells decreases by 30∼200 bp with each cell division. It is generally believed that when telomeres reach a critical length, a signal is activated to initiate the senescent program. This has given rise to the hypothesis that telomeres act as mitotic clocks to regulate lifespan. One proposes that cumulative oxidative stress, mainly reactive oxygen species generated from mitochondria, may mainly cause telomere shortening, accelerating aging. Here, the biological importance and mechanism of replicative senescence were briefly reviewed. Also it was summarized that how oxidative stress affects replicative senescence and telomere shortening.

• 한국동물생명공학회지
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• 제34권2호
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• pp.93-99
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• 2019

Telomeres are known as a specialized region in the end of chromosomes to protect DNA destruction, but their lengths are shortened by repetition of cell division. This telomere shortening can be preserved or be elongated by telomerase and TERT expression. Although a certain condition in the cells may affect to the cellular and molecular characteristics, the effect of differentiation induction to telomere length and telomerase activity in mesenchymal stem cells (MSCs) has been less studied. Therefore, the present study aimed to uncover periodical alterations of telomere length, telomerase activity and TERT expression in the dental pulp-derived MSCs (DP-MSCs) under condition of differentiation inductions into adipocytes and osteoblasts on a weekly basis up to 3 weeks. Shortening of telomere was significantly (p < 0.05) identified from early-middle stages of both differentiations in comparison with undifferentiated DP-MSCs by non-radioactive chemiluminescent assay and qRT-PCR method. Telomere length in undifferentiated DP-MSCs was 10.5 kb, but the late stage of differentiated DP-MSCs which can be regarded as the adult somatic cell exhibited 8.1-8.6 kb. Furthermore, the relative-quantitative telomerase repeat amplification protocol or western blotting presented significant (p < 0.05) decrease of telomerase activity since early stages of differentiations or TERT expression from middle stages of differentiations than undifferentiated state, respectively. Based on these results, it is supposed that shortened telomere length in differentiated DP-MSCs was remained along with prolonged differentiation durations, possibly due to weakened telomerase activity and TERT expression. We expect that the present study contributes on understanding differentiation mechanism of MSCs, and provides standardizing therapeutic strategies in clinical application of MSCs in the animal biotechnology.

• Asian Pacific Journal of Cancer Prevention
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• 제14권2호
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• pp.795-799
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• 2013

Ku70/80 heterodimer is a central element in the nonhomologous end joining (NHEJ) DNA repair pathway, Ku80 playing a key role in regulating the multiple functions of Ku proteins. It has been found that the Ku80 protein located at telomeres is a major contributor to radiosensitivity in some telomerase positive human cancer cells. However, in ALT human osteosarcoma cells, the precise function in radiosensitivity and telomere maintenance is still unknown. The aim of this study was to investigate the effects of Ku80 depletion in the U2OS ALT cell line cell line. Suppression of Ku80 expression was performed using a vector-based shRNA and stable Ku80 knockdown in cells was verified by Western blotting. U2OS cells treated with shRNA-Ku80 showed lower radiobiological parameters (D0, Dq and SF2) in clonogenic assays. Furthermore, shRNA-Ku80 vector transfected cells displayed shortening of the telomere length and showed less expression of TRF2 protein. These results demonstrated that down-regulation of Ku80 can sensitize ALT cells U2OS to radiation, and this radiosensitization is related to telomere length shortening.

• 한국가금학회지
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• 제49권1호
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• pp.15-23
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• 2022

본 연구는 국내 토착화된 닭 12개 품종(재래종 5계통, 한국형 로드종 2계통, 한국형 레그혼종 2계통, 한국형 코니시종 2계통 및 한국오계)의 생리적 활성 정도를 비교하고 자품종 간 텔로미어 길이 및 생존 능력을 분석하였다. 분석에 총 466수를 공시하고 텔로미어 길이는 양적 형광접합보인법을 이용하여 각 개체의 백혈구 세포 내 telomeric DNA의 상대적 함량을 분석하였다. 각 품종의 생존 능력은 발생 후부터 50주령까지의 생존율로 분석하였다. 분석 결과, 모든 품종에서 공히 연령이 증가함에 따라 텔로미어 길이의 선형적 감소를 나타내었고, 품종 간 텔로미어 길이는 20주령 이후부터 유의한 차이를 보이고 동일 기간에 텔로미어 길이의 단축율에도 차이가 있는 것으로 나타났다(P<0.01). 품종 간에 있어서는 한국형 로드-D종이 가장 긴 텔로미어 길이와 가장 낮은 텔로미어 단축율을 보였고, 반면 한국형 코니시 갈색종은 가장 짧은 텔로미어 길이와 가장 높은 단축율을 나타내었다. 텔로미어의 단축 정도는 50주령 텔로미어 길이는 8주령 길이의 절반 정도에 불과한 것으로 나타났다. 생존율에서도 품종 간 유의한 차이를 보이며 한국형 로드종과 오계가 상대적으로 높은 생존율을 보이고, 한국형 코니시종이 가장 저조한 생존율을 나타내었다. 생존율과 텔로미어길이 간에는 유의한 정(+)의 상관을 보이고 성장 초기보다는 노년의 텔로미어 길이가 생존율과 더 높은 상관관계를 나타내었다. 따라서 특정 시기의 텔로미어 길이보다는 일정기간 동안 텔로미어 길이의 단축율이 생존율과 더욱 밀접한 관련이 있는 것으로 사료된다. 이상의 텔로미어 역동성과 생존 능력 분석 결과를 바탕으로 토종닭 품종 중 한국형 로드종의 생리활성도가 가장 높고, 한국형 코니시종의 생리활성도가 가장 낮다고 판단된다.

• Childhood Kidney Diseases
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• 제12권1호
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• pp.11-22
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• 2008

Telomeres consist of tandem guanine-thymine(G-T) repeats in most eukaryotic chromosomes. Human telomeres are predominantly linear, double stranded DNA as they ended in 30-200 nucleotides(bases,b) 3'-overhangs. In DNA replication, removal of the terminal RNA primer from the lagging strand results in a 3'-overhang of uncopied DNA. This is because of bidirectional DNA replication and specificity of unidirectional DNA polymerase. After the replication, parental and daughter DNA strands have unequal lengths due to a combination of the end-replication problem and end-processing events. The gradual chromosome shortening is observed in most somatic cells and eventually leads to cellular senescence. Telomere shortening could be a molecular clock that signals the replicative senescence. The shortening of telomeric ends of human chromosomes, leading to sudden growth arrest, triggers DNA instability as biological switches. In addition, telomere dysfunction may cause chronic allograft nephropathy or kidney cancers. The renal cell carcinoma(RCC) in women may be less aggressive and have less genomic instability than in man. Younger patients with telomere dysfunction are at a higher risk for RCC than older patients. Thus, telomeres maintain the integrity of the genome and are involved in cellular aging and cancer. By studying the telomeric DNA, we may characterize the genetic determinants in diseases and discover the tools in molecular medicine.

• Journal of Korean Biological Nursing Science
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• 제24권4호
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• pp.235-242
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• 2022

Purpose: To investigate associations of perceived stress level, serum cortisol level, and telomere length of community-dwelling adults in Korea. Methods: Data of a total of 135 community-dwelling adults aged over 40 years living in D metropolitan city from December 2020 to March 2021 were collected. Perceived stress level over the past month were measured using the Perceived Stress Score. Serum cortisol level was analyzed using a chemiluminescent microparticle immunoassay. Telomere length was determined using quantitative real-time polymerase chain reaction. The statistical package SPSS 23.0 was used to perform Chi-square test, independent t-test, and Pearson's correlation coefficient analysis. Results: There was no association between perceived stress and serum cortisol level (r = .07, p= .402). Serum cortisol level was not significantly associated with telomere length either (r = -.15, p= .081). However, the higher the perceived stress level, the shorter the telomere length (r= -.29, p= .001). Conclusion: These results suggest that perceived stress might induce physiological stress, which might partially affect gene biology. Further longitudinal research is needed to investigate the effect of perceived stress on telomere length. Intervention for relieving stress should be included in stabilizing the genetic environment of adults.

• Asian-Australasian Journal of Animal Sciences
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• 제24권5호
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• pp.603-609
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• 2011

Telomeres are special structures at the ends of eukaryotic chromosomes. Vertebrate telomeres consist of tandem repeats of conserved TTAGGG sequence and associated proteins. Birds are interesting models for molecular studies on aging and cellular senescence because of their slow aging rates and longer life spans for their body size. In this longitudinal study, we explored the possibility of using telomeres as an age-marker to predict age in Single Comb White Leghorn layer chickens. We quantified the relative amount of telomeric DNA in isolated peripheral blood lymphocytes by the Quantitative Fluorescence in situ Hybridization technique on interphase nuclei (IQ FISH) using telomere-specific DNA probes. We found that the amount of telomeric DNA (ATD) reduced significantly with an increase in chronological age of the chicken. Especially, the telomere shortening rates are greatly increased in growing individuals compared to laying and old-aged individuals. Therefore, using the ATD values obtained by IQ FISH we established the possibility of age prediction in chickens based on the telomere theory of aging. By regression analysis of the ATD values at each age interval, we formulated an equation to predict the age of chickens. In conclusion, the telomeric DNA values by IQ FISH analyses can be used as an effective age-marker in predicting the chronological age of chickens. The study has implications in the breeding and population genetics of poultry, especially the reproductive potential.

• Journal of Photoscience
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• 제9권2호
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• pp.150-153
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• 2002

Solar UV light is a well-known carcinogen. UVA radiation is probably carcinogenic to humans. In addition, recent investigations point to the importance of UVA irradiation in the photoaging. We investigated the mechanism of sequence- specific DNA damage using $\^$32/P-Iabeled DNA fragments in relation to carcinogenesis and aging. Furthermore, we investigated whether UVA accelerates the telomere shortening in human WI-38 fibroblasts. The exposure of double- stranded DNA fragments to 365 nm light in the presence of endogenous sensitizers produced sequence-specific cleavage at the 5' site of 5'-GG-3' and 5'-GGG-3' sequences. In addition, HPLC analysis revealed that sensitizers plus 365 nm light increased the 8-oxodG content of double-stranded DNA. We discuss the mechanisms of guanine-specific DNA damagecaused by excited photosensitizers in relation to carcinogenesis and aging.