• Title/Summary/Keyword: telomere

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Analysis of Telomere Length and Telomerase Activity of Tissues in Korean Native Chicken (한국 재래닭의 주령별 각 조직의 텔로미어 함량과 텔로머레이스 활성도 분석)

  • Jung G.S.;Cho E.J.;Choi D.S.;Lee M.J.;Park C.;Jeon I.S.;Sohn S.H.
    • Korean Journal of Poultry Science
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    • v.33 no.2
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    • pp.97-103
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    • 2006
  • Telomeres are essential for chromosome stability and are related with cell senescence, apoptosis and cancer. Even though telomere length and telomerase activity have been studied extensively, very little is known to analyze the telomere dynamics in chicken cells. This study was carried out to analyze the telomere distribution and telomerase activity of Korean Native Chicken cells along with aging. The cells were collected from brain, heart, liver, kidney and germinal tissues during physiological stages. Telomere distribution was analyzed by Quantitative-Fluorescence in situ Hybridization (Q-FISH) techniques using the chicken telomeric DNA probe. Telomerase activity was performed by Telomeric Repeat Amplification Protocol (TRAP) assay. In results, the telomeres of chicken were found at the ends of all chromosomes with the interstitial telomeres on chromosomes 1, 2 and 3. The amount of telomeres on chicken cells was decreased along with aging in most tissues. Furthermore, the telomere quantity was significantly different among tissues. The relative amount of telomeres in proliferous cells such as testis cells had much more than those of liver, brain, heart, blood and kidney cells. The telomerase activity was down-regulated in cells of brain, heart and liver tissues. Whereas gonadal cells showed a constitutive activity of telomerase during all stage of life. In conclusions, the telomere quantity and telomerase activity in chicken are closely relate to cell proliferation and tissue specificity during developmental stages and aging. There is also closely correlated between the amounts of telomeric DNA and telomerase activity in chicken tissues.

The Relationship of the Expressions of Stress-related Markers and Their Production Performances in Korean Domestic Chicken Breed (닭의 스트레스 연관 표지인자들의 발현도와 생산능력 간의 상관 분석)

  • Park, Ji Ae;Cho, Eun Jung;Choi, Eun Sik;Hong, Yeong Ho;Choi, Yeon Ho;Sohn, Sea Hwan
    • Korean Journal of Poultry Science
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    • v.43 no.3
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    • pp.177-189
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    • 2016
  • This study was conducted to verify the relationships between the expression values of stress-related markers and their production performances in 25 strains of Korean domestic chicken breeds. For stress response markers, the amount of telomeric DNA; expression levels of heat shock protein (HSP)-70, $HSP-90{\alpha}$, and $HSP-90{\beta}$; and comet scores were analyzed. Production performances were measured by the survival rate, body weights, days at first egg laying, egg weight and hen housed egg production. The results showed that the production traits and values of stress-related markers showed significant differences between strains. In general, the stress response of pure bred chickens with heavy weights was relatively high, while that of hybrid chickens with light weights was relatively low. The correlation coefficients between telomere contents and body weights showed that there were weak negative relationships. However, the correlations of telomere content with the survival rate and egg production were weakly positive after 20 weeks old. The expression levels of HSP genes and DNA damage rate (comet scores) were positively correlated to body weight, but were negatively correlated to the survival rate and egg production. The results implied that increasing body weight was associated with increasing HSPs expression and the DNA damage rate was associated with decreasing telomere content. In addition, increasing HSPs expression and the DNA damage rate decreased the survival rate and egg production, but the relationships with the telomere content was the reverse. Correlations among the stress-related markers showed that there were significant correlation coefficients between all of the marker values. HSPs expression was negatively correlated to the telomere content, while it was positively correlated to the DNA damage rate. There was a highly negative correlation between the telomere content and DNA damage rate. In conclusion, increasing the HSP values and DNA damage rate can promote telomere reduction, which led to a decrease in disease resistance and robustness of the chicken. Thus, increasing the stress response was verified to adversely affect the laying performance and viability of chickens.

Kidneys with bad ends (신장 기능과 틸로미어)

  • Suh, Dong-Chul
    • Childhood Kidney Diseases
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    • v.12 no.1
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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.

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THE INFLUENCE OF SOY ISOFLAVON TO THE SKIN AGING IN PRE- MENOPAUSAL WOMEN

  • Subchan, P.;Tranggono, R.I.S.;Djajadisastra, J.
    • Proceedings of the SCSK Conference
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    • 2003.09a
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    • pp.73-84
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    • 2003
  • Skin aging process on pre-menopausal women is a problem that needs to be prevented as early as possible. The decrease of oestrogen level which is one of the intrinsic factors of the skin aging process will affect the skin biological process, due to oestrogen receptors on the skin. A number of researches conducted on pre-menopausal women with the allocation of oestrogen hormone resulted in delaying the skin aging process. The administration of soy isoflavon, a phytoestrogen found in daily food, on pre-menopausal women is hoped to be able to prevent skin aging process, even clinically or molecular biologically. This research aims to explain the benefit of administering of soy isoflavon on skin aging process. The design of the research is randomised controlled trial (RCT). As many as 60 pre-menopausal women were collected with simple random sampling method. Soy isoflavon is an independent variable, while skin aging process is a dependent variable assessed from the hydration, sebum level, average roughness, depth of wrinkles, skin clarity, length of the telomere. Analysis was conducted using t and MANDVA tests and.the result showed a significance (F = 10,439; p = 0,001) over the allocation of soy isoflavon to the whole variable dependent, including the telomere length and the skin hydration, meant that allocation of soy isoflavon could delay skin aging process.

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Regulatory Effects of WRAP53 on Radiosensitivity of Laryngeal Squamous Cell Carcinoma Cells

  • Qiu, Hui;Zhao, De-Ying;Yuan, Li-Mei;Zhang, Gong;Xie, Cong-Hua
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.7
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    • pp.2975-2979
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    • 2015
  • Background: Telomere length is closely associated with cellular radiosensitivity and WRAP53 is required for telomere addition by telomerase. In this research we assessed radiosensitivity of laryngeal squamous cell carcinoma Hep-2 cell lines after WRAP53 inhibition, and analyzed the molecular mechanisms. Materials and Methods: phWRAP53-siRNA and pNeg-siRNA were constructed and transfected into Hep-2 cells with lipofectamine. Expression of WRAP53 was analyzed by RT-PCR and Western-blottin, radiosensitivity of Hep-2 cells was assessed colony formation assay, and the relative length of telomeres was measured by QPCR. Results: The data revealed that the plasmid of phWRAP53-siRNA was constructed successfully, and the mRNA and protein levels of WRAP53 were both obviously reduced in the Hep-2 cell line transfected with phWRAP53-siRNA. After Hep-2 cells were irradiated with X-rays, the $D_0$ and $SF_2$ were 2.481 and 0.472, respectively, in the phWRAP53-siRNA group, much lower than in the control group ($D_0$ and $SF_2$ of 3.213 and 0.592) (P<0.01). The relative telomere length in the phWRAP53-siRNA group was $0.185{\pm}0.01$, much lower than in the untreated group ($0.523{\pm}0.06$) and the control group ($0.435{\pm}0.01$). Conclusions: Decreasing the expression of WRAP53 using RNA interference technique can enhance the radiosensitivity of Hep-2 cell lines by influencing the telomere length. WRAP53 is expected to be a new target to regulate the radiosensitization of tumor cells.

Mechanism of guanine-specific DNA damage by UVA and its role in photocarcinogenesis and photoaging

  • Kawanishi, Shosuke;Oikawa, Shinji;Hiraku, Yusuke
    • Journal of Photoscience
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    • v.9 no.2
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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.

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Implications of telomerase reverse transcriptase in tumor metastasis

  • Zou, Yongkang;Cong, Yu-sheng;Zhou, Junzhi
    • BMB Reports
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    • v.53 no.9
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    • pp.458-465
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    • 2020
  • Metastasis is the main culprit of the great majority of cancerrelated deaths. However, the complicated process of the invasion-metastasis cascade remains the least understood aspect of cancer biology. Telomerase plays a pivotal role in bypassing cellular senescence and sustaining the cancer progression by maintaining telomere homeostasis and genomic integrity. Telomerase reverse transcriptase (TERT) exerts a series of fundamental functions that are independent of its enzymatic cellular activity, including proliferation, inflammation, epithelia-mesenchymal transition (EMT), angiogenesis, DNA repair, and gene expression. Accumulating evidence indicates that TERT may facilitate most steps of the invasion-metastasis cascade. In this review, we summarize important advances that have revealed some of the mechanisms by which TERT facilitates tumor metastasis, providing an update on the non-canonical functions of telomerase beyond telomere maintaining.

Shelterin Proteins and Cancer

  • Patel, Trupti NV;Vasan, Richa;Gupta, Divanshu;Patel, Jay;Trivedi, Manjari
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.8
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    • pp.3085-3090
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    • 2015
  • The telomeric end structures of the DNA are known to contain tandem repeats of TTAGGG sequence bound with specialised protein complex called the "shelterin complex". It comprises six proteins, namely TRF1, TRF2, TIN2, POT1, TPP1 and RAP1. All of these assemble together to form a complex with double strand and single strand DNA repeats at the telomere. Such an association contributes to telomere stability and its protection from undesirable DNA damage control-specific responses. However, any alteration in the structure and function of any of these proteins may lead to undesirable DNA damage responses and thus cellular senescence and death. In our review, we throw light on how mutations in the proteins belonging to the shelterin complex may lead to various malfunctions and ultimately have a role in tumorigenesis and cancer progression.

Nuclease Delivery: Versatile Functions of SLX4/FANCP in Genome Maintenance

  • Kim, Yonghwan
    • Molecules and Cells
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    • v.37 no.8
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    • pp.569-574
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    • 2014
  • As a scaffold, SLX4/FANCP interacts with multiple proteins involved in genome integrity. Although not having recognizable catalytic domains, SLX4 participates in diverse genome maintenance pathways by delivering nucleases where they are needed, and promoting their cooperative execution to prevent genomic instabilities. Physiological importance of SLX4 is emphasized by the identification of causative mutations of SLX4 genes in patients diagnosed with Fanconi anemia (FA), a rare recessive genetic disorder characterized by genomic instability and predisposition to cancers. Recent progress in understanding functional roles of SLX4 has greatly expanded our knowledge in the repair of DNA interstrand crosslinks (ICLs), Holliday junction (HJ) resolution, telomere homeostasis and regulation of DNA damage response induced by replication stress. Here, these diverse functions of SLX4 are reviewed in detail.