• 한국약용작물학회지
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• 제10권4호
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• pp.237-242
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• 2002

It was found that the purified extract from A. gigas Nakai (polysaccharide, M.W., 25 kD) controled differentiating human ES cells. Its optimal supplementation concentration was decided as 0.8 $({\mu}g/ml)$ to efficiently control the differentiation. It also enhanced the cell growth, compared to the control. However, most widely used and commercially available differentiating agent, Leukemia Inhibitory Factor (LIF) negatively affected on the cell growth even though it controls the differentiation of ES cells, down to 40-50 % based on morphological observation and telomerase activity. It was presumed that the extract first affected on cell membrane and resulted in controlling signal system, then amplify gene expression of telomere, which enhanced the telomerase activity up to three times compared to the control. LIF only increased the enzyme activity up to two times. It was confirmed that the extract from A. gigas Nakai could be used for substituting currently used differentiation controlling agent, LIF from animal resources as a cheap plant resource and not affecting the cell growth. It can broaden the application of the plants not only to functional foods and their substitutes but also to fine chemicals and most cutting-edge biopharmaceutical medicine.

• Molecules and Cells
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• 제40권9호
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• pp.607-612
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• 2017

When mammalian cells and animals face a variety of internal or external stresses, they need to make homeostatic changes so as to cope with various stresses. To this end, mammalian cells are equipped with two critical stress responses, autophagy and cellular senescence. Autophagy and cellular senescence share a number of stimuli including telomere shortening, DNA damage, oncogenic stress and oxidative stress, suggesting their intimate relationship. Autophagy is originally thought to suppress cellular senescence by removing damaged macromolecules or organelles, yet recent studies also indicated that autophagy promotes cellular senescence by facilitating the synthesis of senescence-associated secretory proteins. These seemingly opposite roles of autophagy may reflect a complex picture of autophagic regulation on cellular senescence, including different types of autophagy or a unique spatiotemporal activation of autophagy. Thus, a better understanding of autophagy process will lead us to not only elucidate the conundrum how autophagy plays dual roles in the regulation of cellular senescence but also helps the development of new therapeutic strategies for many human diseases associated with cellular senescence. We address the pro-senescence and anti-senescence roles of autophagy while focusing on the potential mechanistic aspects of this complex relationship between autophagy and cellular senescence.

• Biotechnology and Bioprocess Engineering:BBE
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• 제5권1호
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• pp.1-6
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• 2000

For the rapid selection of higher recombinant hirudin producing strain in a methylotrophic yeast Hansenula polymorpha, a multiple gene integration and dose-dependent selection vector, based on a telomere-associated ARS and a bacterial aminoglycoside 3-phosphotransferase (aph) gene, was adopted. Two hirudin expression cassettes (HV1 and HV2) were constructed using the MOX promoter of H. polymorpha and the mating factor $\alpha$ secretion signal of S. cerevisiae. Multiple integrants of a transforming vector containing hirudin expression cassettes were easily selected by using an antibiotic, G418. Hirudin expression level and integrated plasmid copy number of the tested transformants increased with increasing the concentration of G418 used for selection. The expression level of HV1 was consistently higher than that of HV2 under the similar conditions, suggesting that the gene context might be quite important for the high-level gene expression in H. polymorpha. The highest hirudin producing strain selected in this study produced over 96 mg/L of biologically active hirudin in a 500-mL flask and 165 mg/L in a 5-L fermentor.

• Reproductive and Developmental Biology
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• 제30권4호
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• pp.263-270
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• 2006

The Chinese Hamster Ovarian cells CHO-K1 are one of the most extensively used cells for the evaluation of gene expression and toxicology. However, these cells are frequently used for biomedical research without consideration of their cytogenetic characteristics. Therefore, we carried out to investigate the karyologic profiles, the frequency and type of chromosome aberration, and the distribution of telomeric DNA on chromosomes of the CHO-K1 cells. The GTG banding and fluorescence in situ hybridization on CHO-K1 cells were performed to characterize the karyotype and the distribution of telomeric DNA The present study revealed that the chromosome modal number of CHO-K1 cells was 2n=20; eight chromosomes appeared to be identical with those of the normal Chinese hamster, whereas the remaining 12 chromosomes were shown to be translocated, deleted, inversed, or rearranged from Chinese hamster chromosomes. The telomeric DNA on CHO-K1 chromosomes was intensively distributed at the centromeres rather than the ends of chromosomes. In addition, three chromosomes had interstitial telomeres and one marker chromosome entirely consisted of telomeric DNAs. The frequency and type of chromosome aberrations in CHO-K1 cells were examined. Of the 822 metaphase spreads, 68 (8.3%) cells resulted in chromosome aberrations of which the chromosome breakage was the most frequently occurred.

• BMB Reports
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• 제51권1호
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• pp.45-53
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• 2018

Mammalian target of rapamycin complex 1 (mTORC1) plays a major role in cell growth, proliferation, polarity, differentiation, development, and controls transitioning between anabolic and catabolic states of the cell. It collects almost all extracellular and intracellular signals from growth factors, nutrients, and maintains cellular homeostasis, and is involved in several pathological conditions including, neurodegeneration, Type 2 diabetes (T2D), obesity, and cancer. In this review, we summarize current knowledge of upstream signaling of mTORC1 to explain etiology of T2D and hypertriglyceridemia, in which state, the role of telomere attrition is explained. We discuss if chronic inhibition of mTORC1 can reverse adverse effects resulting from hyperactivation. In conclusion, we suggest the regulatory roles of telomerase (TERT) and hexokinase II (HKII) on mTORC1 as possible remedies to treat hyperactivation. The former inhibits mTORC1 under nutrient-rich while the latter under starved condition. We provide an idea of TOS (TOR signaling) motifs that can be used for regulation of mTORC1.

• 대한화장품학회:학술대회논문집
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• 대한화장품학회 2003년도 IFSCC Conference Proceeding Book II
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• pp.117-138
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• 2003

Reactive oxygen species are capable of damaging biomolecules such as lipids, proteins, and DNA, which can not only lead to various diseases, but also oxidative damage resulting aging. In our previous study, Cercis chinensis (Leguminosae) showed a potent antioxidant activity. Nineteen compounds were isolated through antioxidant activity-guided fractionation. The C. chinensis extract and some of the constituents exhibited a potent antioxidant activity on the free radicals and lipid peroxidation and a notable protective effect on the t-BuOOH induced oxidative damage. In vivo test of skin damage induced by UVB irradiation, the extract of C. chinensis and a constituent, piceatannol, exhibited a significant protective effect. The life-span of the HEK-N/F cells were extended by 1.21-2.12 fold as a result of the continuous administration of 3 $\mu\textrm{g}$/ml of the C. chinensis extract and the active constituents compared to that of the control. These observations were attributed to the inhibitory effect of the C. chinensis extract and its constituents on the age-dependent shortening of the telomere. Thus, C. chinensis was demonstrated to protect the skin cells against oxidative stress and inhibit thereby the cellular aging, followed by expectation as antiaging cosmetic ingredient.

• Molecules and Cells
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• 제41권7호
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• pp.684-694
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• 2018

Upregulation of human telomerase reverse transcriptase (hTERT) expression is an important factor in the cellular survival and cancer. Although growing evidence suggests that hTERT inhibits cellular apoptosis by telomere-independent functions, the mechanisms involved are not fully understood. Here, we show that hTERT contains a BH3-like motif, a short peptide sequence found in BCL-2 family proteins, and interacts with anti-apoptotic BCL-2 family proteins MCL-1 and BCL-xL, suggesting a functional link between hTERT and the mitochondrial pathway of apoptosis. Additionally, we propose that hTERT can be categorized into the atypical BH3-only proteins that promote cellular survival, possibly due to the non-canonical interaction between hTERT and antiapoptotic proteins. Although the detailed mechanisms underlying the hTERT BH3-like motif functions and interactions between hTERT and BCL-2 family proteins have not been elucidated, this work proposes a possible connection between hTERT and BCL-2 family members and reconsiders the role of the BH3-like motif as an interaction motif.

• 한방안이비인후피부과학회지
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• 제27권1호
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• pp.45-57
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• 2014

Objective : The purpose of this study is to understand aging and skin aging with both western and Korean medicine. Methods : We investigated the comprehension of general aging and skin aging in both western and Korean medicine through literature review. Result : The results are as follows. 1. Aging in western is a complex process influenced by telomere shortening and damage to cellular DNA. In Korean medicine, it is supposed that decline of interaction between yin(陰) and yang(陽) makes aging. 2. Skin aging in western medicine consists of intrinsic aging and extrinsic aging. In Korean medicine, skin aging goes with the aging of whole body and distinctive features of geroderma notice the unbalance of the whole body function. 3. Generally geroderma has decreased development of cells and low immunity, which is the function of kidney(腎) in Korean medicine. Conclusion : Further studies are needed to apply comprehension of skin aging in Korean medicine to clinical stage.

• BMB Reports
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• 제52권1호
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• pp.24-34
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• 2019

Sirtuin is an essential factor that delays cellular senescence and extends the organismal lifespan through the regulation of diverse cellular processes. Suppression of cellular senescence by Sirtuin is mainly mediated through delaying the age-related telomere attrition, sustaining genome integrity and promotion of DNA damage repair. In addition, Sirtuin modulates the organismal lifespan by interacting with several lifespan regulating signaling pathways including insulin/IGF-1 signaling pathway, AMP-activated protein kinase, and forkhead box O. Although still controversial, it is suggested that the prolongevity effect of Sirtuin is dependent with the level of and with the tissue expression of Sirtuin. Since Sirtuin is also believed to mediate the prolongevity effect of calorie restriction, activators of Sirtuin have attracted the attention of researchers to develop therapeutics for age-related diseases. Resveratrol, a phytochemical rich in the skin of red grapes and wine, has been actively investigated to activate Sirtuin activity with consequent beneficial effects on aging. This article reviews the evidences and controversies regarding the roles of Sirtuin on cellular senescence and lifespan extension, and summarizes the activators of Sirtuin including Sirtuin-activating compounds and compounds that increase the cellular level of nicotinamide dinucleotide.

• 대한의생명과학회지
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• 제28권1호
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• pp.9-24
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• 2022

The aim of this study was to identify the expression of zinc finger E-box binding homeobox 1 (ZEB1), its prognostic significance, and correlation between ZEB1 and infiltrating immune cells in lung cancer. Correlation between ZEB1 and telomerase was also analyzed in different types of cancers. RNA sequencing analysis and survival rates of patients were confirmed by Gene Expression Profiling Interactive Analysis (GEPIA). The Kaplan-Meier plotter and PrognoScan databases were used to analyze the prognostic value of ZEB1 in various cancers. The Tumor IMmune Estimation Resource (TIMER) was used to determine the correlation between ZEB1 and infiltrating immune cells. Lower ZEB1 expression was lower in lung cancer and was related to poor prognosis in lung adenocarcinoma (LUAD). ZEB1 expression exhibited a significantly positive correlation with infiltration levels of immune cells in LUAD and lung squamous cell carcinoma. Furthermore, we found that the ZEB1 expression correlated with subunits of telomerase. Our findings suggest ZEB1 as a potential biomarker to be used for prognostic significance and tumor immunology in lung cancer. The correlation between the expression of ZEB1 and telomere-related gene will help in understand the cancer-promoting mechanisms.