• 혜화의학회지
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• 제21권1호
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• pp.11-21
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• 2012

New onset diabetes is a major complication after kidney transplantation. However, the natural course of posttransplantation diabetes mellitus (PTDM) remains unclear. The aim of this study was to demonstrate the detailed natural courses of PTDM according to the onset and persistency of hyperglycemia, and to investigate risk factors for development of different courses of PTDM in renal allograft recipients. The purpose of this study is to develop novel immune suppressants for PTDM using of action mechanism of them. The use of immunosuppressive drugs in transplanted patients is associated with the development of diabetes, possibly due to ${\beta}$-cell toxicity. To better understand the mechanisms leading to post-transplant diabetes, we investigated the actions of prolonged exposure of ${\beta}$-cells to therapeutical levels of tacrolimus (FK506) or cyclosporin A(CsA). The immunosuppressive drug cyclosporine(CsA) is a potent agent widely used after organ transplantations and various autoimmune disorders. After using CsA, some patients suffer severe complications including renal and vascular toxicity. The renal or vascular toxicity is influenced by the degree of the endothelial damage. FK506(tacrolimus) is a widely used immunosuppressive agent in the treatment of various medical conditions, including autoimmune disease, bone marrow and organ transplantations. We found some interesting clusters and confirmed the feasibility of cDNA microarray in the study of Immunosuppressant. In this study, we investigated gene expression patterns induced by Immunosuppressant in RIN-m5F of rat insulinoma cell line. Gene expressions evaluated using cDNA microarry in two clusters were increased or decreased. this study provides comprehensive comparison of the patterns of gene expression changes induced by CsA and FK506 in ${\beta}$-cells. This study could establish that the mode of action mechanism by which currently used insulin inhibitors inducing PTDM could be elucidated at least in part, which raises the possibility that novel immune suppressive PTDM can be developed. The molecular biological study on PTDM will also contribute the progress in diabetes research field as well as in that of PTDM.

• 한국동물학회지
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• 제36권4호
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• pp.487-495
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• 1993

TRH (Thvrotropin-Releasing Hormone) known to regulate the transcription of the TSH (Thyroid-Stimulating Hormones gene in pituitary cells, but little is understood about the mechanism(sl involved. re present study was attempted to elucidate the role of Ca2+ movement through the voltage-gated channels in the regulation of TSH gene transcription. The c-fos is one of immediate early genes and used as model system for the investigation of signaling pathwavs involved in various stimuli. The changes of c-fos mRNA levels were determined after treatment of various agents using Northern and slot hybridization analysis. The c-fos mRNA was rapidly and transiently induced by TRH (about 3-fold) in GH3 cells and this induction was repressed by calcium chelating agent (EGTA), calcium channel blocker (verapamil) anti protein kinase C inhibitor (aminoacridine). The abilities of forskolin (adenvlate cvclase activators, PMA (protein kinase C activator), and A23187 (calcium ionophore) to affect c-ios gene transcription, either alone or in combination with TRH were tested in the same cells. All of them significantly increased the level of c-fos mRUA. However, no additive relationship was observed in all combined treatments except forskolin. These results suggest that TRH action on the c-fos gene activation is mediated by calcium influx as well as through protein kinase C.

• Biomolecules & Therapeutics
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• 제31권3호
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• pp.241-252
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• 2023

The era of innovative RNA therapies using antisense oligonucleotides (ASOs), siRNAs, and mRNAs is beginning. Since the emergence of the concept of ASOs in 1978, it took more than 20 years before they were developed into drugs for commercial use. Nine ASO drugs have been approved to date. However, they target only rare genetic diseases, and the number of chemistries and mechanisms of action of ASOs are limited. Nevertheless, ASOs are accepted as a powerful modality for next-generation medicines as they can theoretically target all disease-related RNAs, including (undruggable) protein-coding RNAs and non-coding RNAs. In addition, ASOs can not only downregulate but also upregulate gene expression through diverse mechanisms of action. This review summarizes the achievements in medicinal chemistry that enabled the translation of the ASO concept into real drugs, the molecular mechanisms of action of ASOs, the structure-activity relationship of ASO-protein binding, and the pharmacology, pharmacokinetics, and toxicology of ASOs. In addition, it discusses recent advances in medicinal chemistry in improving the therapeutic potential of ASOs by reducing their toxicity and enhancing their cellular uptake.

• Molecular & Cellular Toxicology
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• 제1권4호
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• pp.248-255
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• 2005

To understand the response of cancer cells to anticancer drugs at the gene expression level, we examined the gene expression changes in response to five anticancer drugs, 5-fluorouracil, cytarabine, cisplatin, paclitaxel, and cytochalasin D in NCI-H460 human lung cancer cells. Of the five drugs, 5-fluorouracil had the most distinctive gene expression signature. By clustering genes whose expression changed significantly, we identified three clusters with unique gene expression patterns. The first cluster reflected the up-regulation of gene expression by cisplatin, and included genes involved in cell death and DNA repair. The second cluster pointed to a general reduction of gene expression by most of the anticancer drugs tested. A number of genes in this cluster are involved in signal transduction that is important for communication between cells and reception of extracellular signals. The last cluster represented reduced gene expression in response to 5-fluorouracil, the genes involved being implicated in DNA metabolism, the cell cycle, and RNA processing. Since the gene expression signature of 5-fluorouracil was unique, we investigated it in more detail. Significance analysis of microarray data (SAM) identified 808 genes whose expression was significantly altered by 5-fluorouracil. Among the up-regulated genes, those affecting apoptosis were the most noteworthy. The down-regulated genes were mainly associated with transcription-and translation-related processes which are known targets of 5-fluorouracil. These results suggest that the gene expression signature of an anticancer drug is closely related to its physiological action and the response of caner cells.

• 한국미생물·생명공학회지
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• 제25권6호
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• pp.571-579
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• 1997

For the overproduction of pectate lyase (PL), the recombinant plasmid pl2BS fl which has strong promoter from alkali-tolerent Bacillus sp. YA-14 was used. In order to overexpress the pectate lyase by the action of overlapping strong promoter in pl2BS$\Delta$fl, 1.6 kb of PL gene was inserted into pl2BS$\Delta$fl to form pl2BS$\delta$f1-PL and the enzyme was expressed. But decreased expression efficiency of the PL gene was observed and it was due to the presence of the transcription terminator region on the upstream of the PL gene. The transcription terminator of the PL gene in pl2BS$\delta$f1-PL was removed and the resulting plasmid p12BS$\Delta$fl$\Delta$PL was formed. Bacillus subtilis 207-25 harboring the recombinant plasmid, p12BS$\Delta$fl$\Delta$PL, revealed increased expression efficiency with chloramphenicol induction when cat-86 was used as a reporter gene.

• Asian Pacific Journal of Cancer Prevention
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• 제14권11호
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• pp.6739-6742
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• 2013

Background: Breast cancer is a major health problem worldwide. Olive oil induces apoptosis in some cancer cells due to phenolic compounds like oleuropein. Although oleuropein has anticancer activity, the underlying mechanisms of action remain unknown. The study aimed to assess the mechanism of oleuropin-induced breast cancer cell apoptosis. Materials and Methods: p53, Bcl-2 and Bax gene expression was evaluated by semi-quantitative reverse transcriptase polymerase chain reaction (RT-PCR) in luminal MCF-7 cells. Results: Oleuropein-induced apoptosis was accompanied by up-regulation of both p53 and Bax gene expression levels and down-regulation in Bcl2. Conclusions: Oleuropein induces apoptosis in breast tumour cells via a p53-dependent pathway mediated by Bax and Bcl2 genes. Therefore, oleuropein may have therapeutic potential in breast cancer patients by inducing apoptosis via activation of the p53 pathway.

• 한국가축번식학회지
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• 제26권4호
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• pp.321-328
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• 2002

The hormone resistin is associated with type II diabetes mellitus in rodent model. Resistin impairs glucose tolerance and insulin action. A new class of anti-diabetic drugs were called thiazolidinediones (TZDs) downreguates a resistin. Resistin gene expression is induced during adipocyte differentiation and resistin polypeptide is secreted by adipocytes. But, the correlation between increased adiposity and resistin remains unknown. The objectives of this study was to clone a mouse resistin CDNA and to generate transgenic mice overexpressing mouse resistin gene. The pCMV-mus/resistin gene was prepared from previous recombinant pTargeT$^{TM}$-mus/resistin by digestion of Bgl II, and has used for microin- jection into pronuclei of one cell embryos. Mouse resistin expression was detected in transgenic F$_1$mice by RT-PCR. The transgenic mouse with resistin gene expression has heavier body weight which was measured higher level of plasma glucose than that of normal mouse. And in diet-induced experiments, in fasting group, resistin expression was higher than that of re-feeding group. This result demonstrates that the resistin gene overexpressing mice may be became to obesity and be useful as an animal disease model to be diabetes caused by insulin resistance of resistin.n.

• 약학회지
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• 제41권1호
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• pp.81-85
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• 1997

Ceramide has been suggested as an important mediator of the effects of extracellular agonists on cell growth inhibition, differentiation, apoptosis. However the biochemical sign aling mechanism involved in transducing the effects of ceramide on leukemia cell differentiation is still unclear. In these respects, we examined the regulatory effects of ceramide on c-jun gene expression during differentiation. In U-937 cells. ceramide increased c-jun mRNA levels in a time-dependent manner. The half life, of c-jun mRNA was 30 min. In contrast, inhibition of protein synthesis with cycloheximide in the absence, of transcription with actinomycin D increased the half-life of c-jun mRNA in ceramide-treated U-937 cells to more than 90 min. In order to examine whether ceramide-inhibited c-jun gene expression is regulated through ceramide-activated protein phosphatase (CAPP), a direct target for the action of ceramide, okadaic acid were treated to the cells. Okadaic acid inhibited enhancement of c-jun mRNA induced by C2-ceramide in a dose-dependent manner. These results suggested that ceramide increases c-jun mRNA level during differentiation in U-937 cells and regulates the gene expression on posttranscriptional level. In addition, we provide the evidence that CAPP is involved in ceramide-induced c-jun gene expression in U-937 cells.

• Clinical and Experimental Reproductive Medicine
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• 제26권3호
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• pp.377-381
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• 1999

Objectives: Recent studies, including our own, demonstrated that the novel expression of LH gene in rat gonads and uterus, indicating that the local production and action of the LH-like molecule. In the present study, we investigated whether human uterus also expresses the LH gene. Design: Reverse transcription-polymerase chain reaction (RT-PCR) amplified the cDNA fragments coding $LH_{\beta}$ polypeptide from human endometrium but not from myometrium. Presence of the transcripts for the ${\alpha}$-subunit in human endometrium was also confirmed by RT-PCR. Results: Transcripts for $LH_{\beta}$ subunit were detected in endometrial samples from women with endometriosis. The gene for LH/hCG receptor was expressed in both endometrium and myometrium, showing good agreement with previous studies. Increased level of $LH_{\beta}$ transcript was determined in the endometrium from follicular phase compared to that from luteal phase. Conclusion: Taken together, our findings demonstrated that 1) the genes for LH subunits and LH/hCG receptor are expressed in human uterus, 2) the uterine LH expression was changed during menstrual cycle, suggesting that the uterine LH may playa local role in the control of uterine physiology and function(s).

• Nutritional Sciences
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• 제8권3호
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• pp.175-180
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• 2005

Green tea, which has high polyphenols amount, is thought to have hypocholesterolemic effects. The present study was performed to further examine the hypocholesterolemic action of green tea, especially (-) epigallocatechin gallate (EGCG) for its effect on diet-induced hypercholesterolemia in rats. Male Sprague-Dawley rats (n=15) were fed a green tea-free diet (control), $1.0\%$ green tea catechin (catechin) or $0.5\%$ green tea catechin EGCG for seven weeks. Hypercholesterolemia was induced by adding $1\%$ cholesterol and $0.5\%$ cholic acid to all diets. There was no difference in food intake and body weight gain among the groups. The green tea EGCG treatment led to a significant improvement in plasma levels of total cholesterol, low density lipoprotein (LDL)-cholesterol and high density lipoprotein (HDL)/LDL ratio (p<0.05). There was no significant effect on the plasma HDL-cholesterol level. The catechin treatment led to a 4.19-fold increase in the LDL-receptor mRNA level compared to the control, but the EGCG treatment did not affect the hepatic LDL-receptor mRNA level. Our results suggest that when blood cholesterol level is down-regulated by green tea EGCG, the LDL receptor gene-independent pathway may dominate the hypocholesterolemic action of EGCG.