• 한국인삼전략화협의회:학술대회논문집
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• 한국인삼전략화협의회 2003년도 제4차 한국인삼약초산업 전략화 세미나
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• pp.54-63
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• 2003

"Korea ginseng (Panax ginseng C.A Meyer) is an important medicinal plant. Its root has been used as an herbal medicine that provides resistance to stress and disease, and prevents exhaustion since the ancient time. Ginsenosides, glycosylated triterpene (saponin), are considered to be the main active compounds of the ginseng root. Despite of considerable commercial interests of ginsenosides, very little is known about the genes and their biochemical pathways for ginsenoside biosynthesis. This work will focus on the identification of genes involved in ginsenoside biosynthesis and the dissection of ginsenoside biosynthetic pathway using a functional genomics tool. Expression sequence tags (ESTs) provide a valuable tool to discovery the genes in secondary metabolite biosynthesis. We generated over 21,155 ginseng ESTs that is now sufficient to facilitate discovering the genes involved in ginsenoside biosynthesis such as oxidosqualene cyclase(OSC), cytochrome P450 and glycosyltransferase. With ESTs information, microarray technology will be used for the analysis of gene expression, and the identification of genes including transcription factors expressed in tissues under given experimental condition. Heterogous system such as yeast and plants will allow us to do the functional analysis. And selected ginseng hairy root which show variation in ginsenoside production will be used as a material for functional analysis of candidate gene. Functional genomics approach will successfully accelerate gene discovery, and also provide promises of metabolic engineering for the ginsenoside production."

• 한국환경농학회지
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• 제37권4호
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• pp.324-332
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• 2018

곤충은 변온동물로 육지생태계에서 주로 서식하면서, 식물의 생체량 조절, 종다양성 유지에 중요한 역할을 한다. 주변온도는 변온동물인 곤충의 생리적 반응속도, 뿐만 아니라 생존과 분포를 결정하며, 기후변화에 영향을 준다. 본 연구는 높은 온도에서 곤충의 적응성에 관련있는 유전자를 전사체를 이용하여 동정하였다. 고온에서 사육된 배추좀나방 유충의 지방체로부터 차세대 염기서열 분석법을 이용하여 전사체를 확보하였다. 대사중심인 지방체에서 구조단백질, 열충격단백질, 항산화단백질, 해독효소 들이 동정되었다. 이들 중에서 표피단백질(표피단백질, 키틴합성효소, 엑틴, 카이틴 합성), 스트레스관련단백질(시토크롬 P450), 열충격단백질, 한산화단백질은 발현이 증가되었으나, glutathione S transferase 발현은 오히려 감소되었다. 이상의 결과는 기후변화의 주요인인 온난화에 대한 해충의 생리적 대응과 온도적응을 이해하는데 필요한 기초자료를 제시한다.

• 한국환경성돌연변이발암원학회지
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• 제25권4호
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• pp.134-142
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• 2005

Liver cancer is a leading cause of tumor-related mortality, Diethylnitrosamine (DEN) is one of the most extensively studied hepatic carcinogens to date. In this study, the mRNA expression profile in DEN-induced liver tumors in mice was analyzed using DNA microarrays. We report increased expression of genes that participate in hypoxia response, including metallothionein 1 (Mt1), metallothionein 2 (Mt2), fatty acid synthase (Fasn), transferrin (Trf), adipose differentiation-related Protein (AdfP) and ceruloplasmin (CP), as well as those involved in predisposition and development of cancers, such as cytochrome P450 2A5 (Cyp2a5), alpha 2-HS-glycoprotein (Ahsg) and Jun-B oncogene (Junb). The hepatic iron regulatory peptide, hepcidin (Hampl), was downregulated in DEN-stimulated liver tumors. Expression of tumor suppressor genes, such as tripartite motif protein 13 (Trim13), was decreased under these conditions. The data collectively indicate that DEN-induced tumor development can be exploited as a possible model for liver cancer, since this process involves various genes with important functions in hepatic carcinogenesis.

• Archives of Pharmacal Research
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• 제27권4호
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• pp.415-421
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• 2004

Cytochrome P450 3A4 (CYP3A4) is the most abundant CYPs in human liver, comprising approximately $30\%$ of the total liver CYPs contents and is involved in the metabolism of more than $60\%$ of currently used therapeutic drugs. However, the molecular mechanisms underly-ing regulation of CYP3A4 gene expression have not been understood. Thus, this study has been carried out to gain the insight of the molecular mechanism of CYP3A4 gene expression, investigating if the histone deacetylation is involved in the regulation of CYP3A4 gene expression by proximal promoter. Also SXR was investigated to see if they were involved in the regulation of CYP3A4 proximal promoter activity. Hepa-1 cells were transfected with a plasmid containing ${\~}1kb$ of the human CYP3A4 proximal promoter region (863 to +64 bp) cloned in front of a reporter gene, luciferase, in the presence or absence of SXR. Transfected cells were treated with CYP3A4 inducers such as rifampicin, PCN and RU 486, in order to examine the regulation of CYP3A4 gene expression in the presence or absence of trichostatin A (TSA). In Hepa-1 cells, CYP3A4 inducers increased modestly the luciferase activity when TSA was co-treated, but this increment was not enhanced by SXR cotransfection. Taken together, these results indicated that the inhibition of histone deacetylation was required to SXR-mediated increase in CYP3A4 proximal promoter region when rifampicin, or PCN was treated. Further a trans-activation by SXR may demand other species-specific transcription factors.

• Asian Pacific Journal of Cancer Prevention
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• 제14권12호
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• pp.7187-7191
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• 2013

Most of the exogenous and endogenous chemical compounds are metabolized by enzymes of xenobiotic processing pathways, including the phase I cytochrome p450 species. Carcinogens and their metabolites are generally detoxified by phase II enzymes like glutathione-S-transferases (GST). The balance of enzymes determines whether metabolic activation of pro-carcinogens or inactivation of carcinogens occurs. Under certain conditions, deregulated expression of xenobiotic enzymes may also convert endogenous substrates to metabolites that can facilitate DNA adduct formation and ultimately lead to cancer development. In this study, we aimed to test the association between deregulation of metabolizing genes and brain tumorigenesis. The expression profile of metabolizing genes CYP1A1 and GSTP1 was therefore studied in a cohort of 36 brain tumor patients and controls using Western blotting. In a second part of the study we analyzed protein expression of GSTs in the same study cohort by ELISA. CYP1A1 expression was found to be significantly high (p<0.001) in brain tumor as compared to the normal tissues, with ~4 fold (OR=4, 95%CI=0.43-37) increase in some cases. In contrast, the expression of GSTP1 was found to be significantly low in brain tumor tissues as compared to the controls (p<0.02). This down regulation was significantly higher (OR=0.05, 95%CI=0.006-0.51; p<0.007) in certain grades of lesions. Furthermore, GSTs levels were significantly down-regulated (p<0.014) in brain tumor patients compared to controls. Statistically significant decrease in GST levels was observed in the more advanced lesions (III-IV, p<0.005) as compared to the early tissue grades (I-II). Thus, altered expression of these xenobiotic metabolizing genes may be involved in brain tumor development in Pakistani population. Investigation of expression of these genes may provide information not only for the prediction of individual cancer risk but also for the prevention of cancer.

• Journal of Animal Science and Technology
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• 제63권6호
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• pp.1247-1264
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• 2021

Anabolic steroids are frequently used to increase the growth rate of meat-producing animals. Exposure to an anabolic-androgenic steroid, nandrolone decanoate (ND), is associated with expressional reduction of testicular steroidogenic enzymes. However, the effect of withdrawal of ND exposure on the expression of these testicular molecules has not been thoroughly explored. The current research investigated expression changes of testicular steroidogenic enzymes in rats at several recovery periods (2, 6, and 12 weeks) after the stop of ND treatment with different doses (2 and 10 mg/kg body weight) for 12 weeks. Body and testis weights were recorded, and transcript levels of molecules were determined by quantitative real-time polymerase chain reaction (PCR). The immunohistochemistry was used to examine the changes of immuno-intensities of molecules. At 6 and 12 weeks of the recovery period, the 10 mg/kg ND-treated rats were lighter than other experimental groups. The interstitial compartment vanished by ND treatment filled up as the recovery period became longer. The expression of steroidogenic acute regulatory protein was returned to the control level at 12 weeks of the recovery period. Expression levels of cytochrome P450 side-chain cleavage and 17a-hydroxylase were increased in 2 mg/kg ND-treated group at 6 weeks of the recovery period, and transcript levels of these molecules in 2 and 10 mg/kg ND-treated groups at 12 weeks of the recovery period were significantly lower than the control. Expression levels of 3β-hydroxysteroid dehydrogenase (HSD) type I and 17β-HSD type 3 in 2 mg/kg ND-treated group were comparable with those of control at 12 weeks of the recovery period, but not in 10 mg/kg ND-treated group. Expression of cytochrome P450 aromatase (Cyp19) was reverted to the control level at 2 weeks of the recovery period. Except for Cyp19, there was a visible increase of immuno-staining intensity of other testicular steroidogenic enzymes in the Leydig cells as the recovery period progressed. This research has demonstrated that the cease of ND administration could restore the expression of testicular steroidogenic enzymes close to the normal level. Nevertheless, a relatively long recovery period, compared to the ND-exposure period would be required to retrieve normal expression levels of testicular steroidogenic enzymes.

• Journal of Acupuncture Research
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• 제20권4호
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• pp.85-92
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• 2003

목적 : 허혈시 발생되는 저산소중 상태에서는 세포독성을 유발한다고 알려져 있으나 정확한 기전은 아직 규명되지 않았다. 본 연구에서는 뇌허혈로 인한 세포독성의 기전을 유전자 발현을 통하여 살펴보고자 하였다. 방법 : 본 실험에서는 BV-2 microglia 세포주에 12시간 동안의 저산소 상태에서의 유전자 발현을 분석하기 위하여 마이크로에레이를 시행하였다. 결과 : 저산소 상태에서는 정상에 비하여 cathepsin F, growth factor independent 1, calcitonin/calcitonin-related poly, leucine-rich repeat LGI family membrane, dublecortin, cyclohydrolase 1, Ia-associated invariant chain, carbohydrate kinase-like과 erythrocyte protein band 4.1-like 3 등의 유전자 발현이 3배 이상 증가하였다. 한편 neuronal guanine nucleotide exchange factor, Bcl-2-related ovarian killer protein, chemokine (C-X-C motif) ligand 5, RNA binding motif protein 3, interleukin 2 receptor, alpha chain, crystallin zeta, cytochrome P450 subfamily IV B, asparagine synthetase과 moesin 등의 유전자 발현은 0.2배 이하로 감소하였다. 결론 : 이상의 결과는 저산소중에 관여하는 유전자 및 저산소중과 관련된 뇌경색 등의 질환의 기전을 밝히는데 기초적 자료로 이용될 수 있을 것이다.

• Molecular & Cellular Toxicology
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• 제1권4호
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• pp.268-274
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• 2005

Bromobenzene (BB) is well known hepatotoxicant. Also, BB is an industrial solvent that arouses toxicity predominantly in the liver where it causes centrilobular necrosis. BB is subjected to Cytochrome P450 mediated epoxidation followed by either conjugation with glutathione, enzymatic hydrolysis or further oxidation. In this study, we focused on BB-induced gene expression at non-hepatotoxic dose. Mice were exposed to two levels of BB, sampled at 24 h, and hepatic gene expression levels were determined to evaluate dose dependent changes. When examining the toxic dose of BB treated group in other previous studies, genes related to heat shock protein, oxidative stress, and drug metabolism are expressed. Compared to these results, our study, in which non-toxic dose of BB was administrated, showed similar patterns as the toxic conditions above. The purpose of the study was to select genes that showed changes in relation to the differing dose through confirmation of the difference within transcriptomic boundaries, but those that are not detected by the existing classic toxicology tools in non-hepatotoxic dose.

• Molecular & Cellular Toxicology
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• 제3권4호
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• pp.267-272
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• 2007

Environmental and anthropogenic changes affect the health and stability of marine ecosystem. In this study we aimed to identify molecular biomarkers for ecotoxicological pollutants risk assessment in the rockfish (Sebastes schlegeli). We designed primers based on conserved sequences by multiple alignments of target genes from related species, and cloned the partial cDNAs of cytochrome P450 (CYP1A1), glutathione S-transferase (GST), metallothionein (MT), superoxide dismutase (SOD), ubiquitin (UB), vitellogenin (VTG) and $\beta$-actin by reverse transcription polymerase chain reaction (RT-PCR) from S. schlegeli. Northern blot results indicated that these six genes expressions were significantly induced by benzo[a]pyrene (BaP, 1 ${\mu}M$) and that the level of each of their transcripts increased in BaP-exposed rockfish in a time-dependent manner. This study suggests that transcriptional changes in these six genes may be used for monitoring environmental exposure to polycyclic aromatic hydrocarbons (PAHs).

• 대한의생명과학회지
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• 제18권1호
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• pp.1-9
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• 2012

Differentially expressed genes by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) were identified in order to evaluate them as dioxin-sensitive markers and crucial signaling molecules to understand dioxin-induced toxic mechanisms in human bronchial cells. Gene expression profiling was analyzed by cDNA microarray and ten genes were selected for further study. They were cytochrome P450, family 1, subfamily B, polypeptide 1 (CYP1B1), S100 calcium binding protein A8 (calgranulin A), S100 calcium binding protein A9 (calgranulin B), aldehyde dehydrogenase 1 family, member A3 (ALDH6) and peroxiredoxin 5 (PRDX5) in up-regulated group. Among them, CYP1B1 was used as a hallmark for dioxin and sharply increased by TCDD exposure. Down-regulated genes were IK cytokine, interferon-induced protein with tetratricopeptide repeats 1 (IFIT1), nuclease sensitive element binding protein 1 (NSEP1), protein tyrosine phosphatase type VI A, member 1 (PTP4A1), ras oncogene family 32 (RAB32). Although up-regulated 4 genes in microarray were coincided with northern hybridization, down-regulated 5 genes showed U-shaped expression pattern which is sharply decreased at lower doses and gradually increased at higher doses. These results introduce some of TCDD-responsive genes can be sensitive markers against TCDD exposure and used as signaling cues to understand toxicity initiated by TCDD inhalation in pulmonary tissues.