• Title/Summary/Keyword: GENE FLOW

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Nrf2 Expression and Apoptosis in Quercetin-treated Malignant Mesothelioma Cells

  • Lee, Yoon-Jin;Lee, David M.;Lee, Sang-Han
    • Molecules and Cells
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    • v.38 no.5
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    • pp.416-425
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    • 2015
  • NF-E2-related factor 2 (Nrf2), a basic leucine zipper transcription factor, has recently received a great deal of attention as an important molecule that enhances antioxidative defenses and induces resistance to chemotherapy or radiotherapy. In this study, we investigated the apoptosis-inducing and Nrf2- upregulating effects of quercetin on malignant mesothelioma (MM) MSTO-211H and H2452 cells. Quercetin treatment inhibited cell growth and led to upregulation of Nrf2 at both the mRNA and protein levels without altering the ubiquitination and extending the half-life of the Nrf2 protein. Following treatment with quercetin, analyses of the nuclear level of Nrf2, Nrf2 antioxidant response element-binding assay, Nrf2 promoter-luc assay, and RT-PCR toward the Nrf2-regulated gene, heme oxygenase-1, demonstrated that the induced Nrf2 is transcriptionally active. Knockdown of Nrf2 expression with siRNA enhanced cytotoxicity due to the induction of apoptosis, as evidenced by an increase in the level of proapoptotic Bax, a decrease in the level of antiapoptotic Bcl-2 with enhanced cleavage of caspase-3 and PARP proteins, the appearance of a sub-$G_0/G_1$ peak in the flow cytometric assay, and increased percentage of apoptotic propensities in the annexin V binding assay. Effective reversal of apoptosis was observed following pretreatment with the pan-caspase inhibitor Z-VAD. Moreover, Nrf2 knockdown exhibited increased sensitivity to the anticancer drug, cisplatin, presumably by potentiating the oxidative stress induced by cisplatin. Collectively, our data demonstrate the importance of Nrf2 in cytoprotection, survival, and drug resistance with implications for the potential significance of targeting Nrf2 as a promising strategy for overcoming resistance to chemotherapeutics in MM.

Genetic Variation of Alien Invasive Red Clover (Trifolium pratense) in Korea (붉은토끼풀의 유전적 변이와 집단구조)

  • Huh Man Kyu;Chung Kyung-Tae;Jeong Yong-Kee
    • Journal of Life Science
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    • v.15 no.2 s.69
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    • pp.273-278
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    • 2005
  • Trifolium pratense (red clover, Fabaceae) is a short-lived herbaceous species and the species is introduced from Europe or North America to Korea approximately 60 years ago. Allozyme variability was examined in populations representing this species. A high level of genetic variation was found in T. pratense populations. Ten of 19 loci $(52.6\%)$ showed detectable polymorphism. Genetic diversity was 0.220. The sexual reproduction, high fecundity, and colonization process are proposed as possible factors contributing to high genetic diversity. Genetic diversity (0.220) was lower than that (0.285) of North American red clover, T. pratense. Korean populations of red clover may be founded by a small sample of larger or moderate populations. An indirect estimate of the number of migrants per generation (Nm = 4.20) indicated that gene flow was extensive among Korean populations of this species.

Comparison of Genetic Diversity and Relationships of Genus Kalopanax Using ISSR Markers (ISSR을 이용한 음나무속 분류군의 유전적 다양성과 관련성 비교)

  • Huh, Man-Kyu
    • Journal of Life Science
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    • v.16 no.5
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    • pp.740-745
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    • 2006
  • Inter simple sequence repeat (ISSR) markers were performed in order to analyse the phylogenetic relationships of four taxa of Castor-aralia (Kalopanax pictus): K. pictus, K. pictus var. magnificus, K. pictus var. maximowiczii, and thornless K. pictus. The 11 primers were produced 64 reproducible ISSR bands. Analysis of ISSR from individual plants of Korean K. pictus resulted in 41 polymorphic bands with 64.1%. When species were grouped by four taxa, within group diversity was 0.115 $(H_S)$, while among group diversity was 0.467 $(G_{ST})$ on a per locus basis. The estimated gene flow (Nm) for K. pictus var. maximowiczii and K. pictus var. magnificus were very higher than K. pictus. It is suggested that the isolation of geographical distance and reproductive isolation among K. pictus populations may have played roles in shaping the population structure of this species. In phenetic tree, ISSR markers are very effective in classifying natural populations as well as taxon levels of genus Kalopanax in Korea.

Anti-Cancer Effect of IN-2001 in T47D Human Breast Cancer

  • Joung, Ki-Eun;Min, Kyung-Nan;Kim, Dae-Kee;Sheen, Yhun-Yhong
    • Biomolecules & Therapeutics
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    • v.20 no.1
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    • pp.81-88
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    • 2012
  • Histone deacetylases (HDACs) are enzymes involved in the remodelling of chromatin, and have a key role in the epigenetic regulation of gene expression. Histone deacetylase (HDAC) inhibitors are emerging as an exciting new class of potential anti-cancer agents. In recent years, a number of structurally diverse HDAC inhibitors have been identifi ed and these HDAC inhibitors induce growth arrest, differentiation and/or apoptosis of cancer cells in vitro and in vivo. However, the underlying molecular mechanisms remain unclear. This study aimed at investigating the anti-tumor activity of various HDAC inhibitors, IN-2001, using T47D human breast cancer cells. Moreover, the possible mechanism by which HDAC inhibitors exhibit anti-tumor activity was also explored. In estrogen receptor positive T47D cells, IN-2001, HDAC inhibitor showed anti-proliferative effects in dose-and time-dependent manner. In T47D human breast cancer cells showed anti-tumor activity of IN-2001 and the growth inhibitory effects of IN-2001 were related to the cell cycle arrest and induction of apoptosis. Flow cytometry studies revealed that IN-2001 showed accumulation of cells at $G_2$/M phase. At the same time, IN-2001 treatment time-dependently increased sub-$G_1$ population, representing apoptotic cells. IN-2001-mediated cell cycle arrest was associated with induction of cdk inhibitor expression. In T47D cells, IN-2001 as well as other HDAC inhibitors treatment significantly increased $p21^{WAF1}$ and $p27^{KIP1}$ expression. In addition, thymidylate synthase, an essential enzyme for DNA replication and repair, was down-regulated by IN-2001 and other HDAC inhibitors in the T47D human breast cancer cells. In summary, IN-2001 with a higher potency than other HDAC inhibitors induced growth inhibition, cell cycle arrest, and eventual apoptosis in human breast cancer possibly through modulation of cell cycle and apoptosis regulatory proteins, such as cdk inhibitors, cyclins, and thymidylate synthase.

Adsorption Characteristics of Strong Basic Anion Exchanger to Cellulose Reactive Dye (강 염기성 음이온 교환수지의 셀룰로우스 섬유용 반응성 염료에 대한 흡착 특성)

  • Lim, Gyeong-Eun;Chung, Paul-gene;Kwon, Ji-Young
    • Journal of Korean Society on Water Environment
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    • v.23 no.1
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    • pp.27-32
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    • 2007
  • This study focused on estimating the feasibility of a strong basic anion exchanger (PA312OH) as a sorbent for the removal of residual reactive dye and saving chemicals and water. Cellulose reactive dye C.I.RB49 was tested because reactive dye is the largest single group of dyes and that dye needs larger amount of inorganic salts as dyeing agent but nearly 50% of reactive dyes may be lost to the effluent. The adsorption characteristics of PA312OH for C.I.RB49 were as follows. Ion-selectivity among the dye and inorganic salts was Dye > ${SO_4}^{2-}$ > ${CO_3}^{2-}$ > $Cl^-$. C.I.RB49 was exchanged more than 3 times ${SO_4}^{2-}$ and ${CO_3}^{2-}$ and $Cl^-$ was not exchanged absolutely. The exchanging velocity was increased exponentially with increasing temperature. This result is positive effect on treating the high temperature dyeing process wastewater. The exchanged dye percents to initial were 96.8% and 99% at flow rate 20.5 mL/min. and 3.7 mL/min.. The exchanging capacity of PA312OH for C.I.RB49 was 215.2 mg/g at conc.=369.2 mg/L, Temp.=$25^{\circ}C$. 74% inorganic salts were recrystallized from real dark reactive color dyeing wastewater treated with PA312OH.

Genetic Diversity and Population Structure of Chimaphila japonica in Southern Part of Korea (한국 남부지역의 매화노루발의 유전적 다양성과 집단구조)

  • Joo-Soo Choi;Man-Kyu Huh
    • Journal of Life Science
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    • v.8 no.6
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    • pp.687-694
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    • 1998
  • Enzyme electrophoresis was used to estimate genetic diversity and population structure of Chimaphila japonica Miq. in Korea. The percent of polymorphic loci within the enzymes was 48.7%. Genetic diversity at the species level and at the population level was high (Hes=0.278 ; Hep=0.222, respectively), whereas the extent of the population divergence was relatively low ( $G_{ST}$ =0.079). $F_{IS}$ , a measure of the deviation from random mating within the 7 populations, was 0.355. An indirect estimate of the number of migrants per generation (Nm=2.61) indicates that gene flow is high among Korean populations of the species. In addition, analysis of fixation indices revealed a substantial heterozygosity deficiency in some populations and at some loci. Factors contributing to the high levels of genetic dive-rsity found in the entire species of C. japonica include wide distribution, long-lived perennials, ability to regenerate due to rhizomatous spread, outcrossing induced by animal vectors, and occasional pollen dispersal by wind.

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Teucrium polium L. Improved Heart Function and Inhibited Myocardial Apoptosis in Isolated Rat Heart Following Ischemia-Reperfusion Injury

  • Mahmoudabady, Maryam;Talebian, Faezeh Sadat;Zabihi, Narges Amel;Rezaee, Seyed Abdolrahim;Niazmand, Saeed
    • Journal of Pharmacopuncture
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    • v.21 no.3
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    • pp.159-167
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    • 2018
  • Objectives: Myocardial reperfusion is the only logical cure for ischemic heart disease. However, ischemic-reperfusion (I/R) injury is one of the underlying factors facilitating and accelerating the apoptosis in the myocardium. This study set to investigate the impact of Teucrium polium (TP) hydro-alcoholic extract on I/R induced apoptosis in the isolated rat heart. Methods: Isolated rat hearts were classified into six groups. The control samples were subjected to 80 min of perfusion with Krebs-Henseleit bicarbonate (KHB) buffer; in control-ischemia group, after primary perfusion (20 min) the hearts were exposed to global ischemia (20 min) and reperfusion (40 min). Pretreated groups were perfused with $500{\mu}M$ of vitamin C and various TP concentrations (0.5, 1, 2 mg/ml) for 20 min, and then the hearts were exposed to ischemia and reperfusion for 20 min and 40 min, respectively. Cardiodynamic parameters including rate pressure product (RPP), heart rate (HR), the maximum up/down rate of left ventricular pressure (${\pm}dp/dt$), left ventricular developed pressure (LVDP), and coronary artery flow (CF) were achieved from Lab Chart software data. The Bax and BCl-2 gene expressions were measured in heart samples. Results: Hearts treated with TP extract and vit C represented a meaningful improvement in cardiac contractile function and CF. The overexpression of Bcl-2, downregulation of Bax, and improvement of apoptotic index (Bax/Bcl-2) were observed in pretreated TP extract and vit C hearts. Conclusion: The TP extract was found to ameliorate the cardiac function in the reperfused myocardium. Also, it can hinder apoptotic pathways causing cardioprotection.

Population Genetic Structure of Potentilla discolor Bunge, Rosaceae in Korea (한국내 솜양지꽃의 집단 유전 구조)

  • Huh, Man-Kyu
    • Journal of Life Science
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    • v.16 no.6
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    • pp.898-903
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    • 2006
  • The genetic diversity and population structure of fifteen Potentilla discolor Bunge populations in Korea were determined using genetic variations at 19 allozyme loci. Fourteen of the 19 loci (73.7%) showed detectable polymorphism. Genetic diversity at the species level and at the population level was high ($H_{ES}\;=\;0.215$, $H_{EP}\;=\;0.196$, respectively), whereas the extent of the population divergence was relatively low $(G_{ST}\;=\;0.069)$. Total genetic diversity values $(H_T)$ varied between 0.0 and 0.656, giving an average overall polymorphic loci of 0.292. The interlocus variation of genetic diversity within populations $(H_S)$ was high (0.274). On a per locus basis, the proportion of total genetic variation due to differences among populations $(G_{ST})$ ranged from 0.010 for Pgm-2 to 0.261 for Pgd-2 with a mean of 0.069, indicating that about 6.9% of the total allozyme variation was among populations. Wide geographic ranges, perennial herbaceous nature and the persistence of multiple generations are associated with the high level of genetic variation in P. discolor. The estimate of gene flow based on $G_{ST}$ was high among Korean populations of P. discolor (Nm = 3.36).

Spatial Autocorrelation within a Korean Population of Alnus hirsuta (한국내 물오리나무(Ainus hirsuta) 집단의 공간적 상관관계)

  • Park, Joo-Soo
    • Journal of Life Science
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    • v.14 no.2
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    • pp.345-350
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    • 2004
  • The present study was investigated microgeographic variations to spatial autocorrelation in the Korean alder, Alnus hirsuta. Separate counts of each type of join (combination of genotypes at a single locus) for each allele, and for each distance class of separation, were tested for significant deviation from random expectations by calculating the Standard Normal Deviation (SND). Moran's I was significantly different from the expected value in 24 of 120 cases (20.0%). 17 of these values (14.2%) were significantly negative, indicating genetic dissimilarity among pairs of individuals in the ten distance classes. Many Korean populations of alder are small and are distributed by men for firewood. This occasional cutting of seed-bearing stems may bring a high level of gene flow. In addition, stump sprouting ability also may contribute to the fact that the Chengkwang population at Gijang is unusual in lacking spatial genetic structure.

Genetic Diversity and Phylogenetic Relationship of Genus Phyllostachys by RAPD Markers (RAPD분자 마커를 이용한 왕대속 대나무의 유전적 다양성 및 계통 관계)

  • Lee, Song-Jin;Huh, Man-Kyu;Shin, Hyun-Cheol;Huh, Hong-Wook
    • Journal of Life Science
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    • v.20 no.6
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    • pp.819-824
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    • 2010
  • Genus Phyllostachys is a long-lived woody species primarily distributed throughout South East Asia. Many species of this genus has been regarded as medically and ecologically important in the world. We evaluated representative samples of the four taxa with RAPD to estimate genetic relationships within the genus Phyllostachys. The percentages of polymorphic loci were 8.9-33.3% at the species level. P. bambusoides was found to show lower genetic diversity (H=0.018) than other species. Total genetic diversity ($H_T$) was 0.315, genetic diversity within populations ($H_S$) was 0.043, the proportion of total genetic diversity partitioned among populations ($G_{ST}$) was 0.659 and the gene flow (Nm) was 0.0263. As some Korean populations were isolated and patchily distributed, they exhibited low levels of genetic diversity. The four taxa of the genus Phyllostachys analyzed were distinctly related to a monophyletic. P. nigra var. henonis. Stapf was found to be more closely related to P. pubescens than to P. nigra. P. bambusoides was quite distinct from the remaining species.