• Journal of mucopolysaccharidosis and rare diseases
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• v.2 no.2
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• pp.46-49
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• 2016

Achondroplasia is autosomal dominant genetic disease and fibroblast growth factor receptor 3 (FGFR3) is currently known to be the only gene that causes achondroplasia. Gain-of function mutation in fibroblast-growth-factor-receptor 3 (FGFR3) causes the disease and C-type natriuretic peptide (CNP) antagonizes FGFR3 downstream signaling by inhibiting the pathway of mitogen-activated protein kinase (MAPK). As FGFR3-related skeletal dysplasias are caused by growth attenuation of the cartilage, chondrocytes appear to be unique in their response to FGFR3 activation. However, the full spectrum of molecular events by which FGFR3 mediates its signaling is just beginning to emerge. This article summaries the mechanisms of FGFR3 function in skeletal dysplasias, the extraordinary cellular manifestations of FGFR3 signaling in chondrocytes, and finally, the progress toward therapy for ACH.

• Proceedings of the PSK Conference
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• 2002.10a
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• pp.291.2-291.2
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• 2002

For the safety evaluation of adenovirus-mediated gene therapy. we have investigated gene and protein expression after transduction of adenoviral vector (Ad5CMV-p16) which contains tumor suppressor gene. p161NK4$\alpha$ in human non-small cell lung cancer (A549) cells. We compared the differential gene expression level in the A549 cells treated with Ad5CMV (null type) and Ad5CMV-p16 virus. respectively. by using cDNA membrane chip and oligonucleotide chip. (omitted)

• Animal cells and systems
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• v.1 no.2
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• pp.389-394
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• 1997

We examined the effect of modulation of PKA isozymes on the growth of human ovarian cancer cells. Three ovarian cancer cell lines, 2774, SK-OV-3, and OVCAR-3, were examined in this study. The treatment of 5 uM 8-CI-cAMP, which has been known to down-regulate RI (or type 1 PKA) and up-regulate RII (or type II PKA), markedly inhibited the growth of all cell lines (50-80% at day 6). To test whether alteration in PKA regulatory subunits level can change the growth characteristics of ovarian cancer cells, we introduced RIIB- expression construct and Rla antisense-expression construct into 2774 cells. The overexpression of RIIB down-regulated Rla protein, and the antisense-expression of Rla up-regulated RIIB protein, showing that the intracellular levels of RI and RII are reciprocally regulated. In both cases, cell growth was reduced by 30% at day 2. These results indicate that the growth of ovarian cancer cells is controlled by the signals from PKA isozymes, and the modulation of PKA isozymes can be employed for the human ovarian cancer therapy.

• Biomolecules & Therapeutics
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• v.21 no.2
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• pp.97-106
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• 2013

Chronic hepatitis C virus (HCV) infection is responsible for the development of liver cirrhosis and hepatocellular carcinoma. HCV core protein plays not only a structural role in the virion morphogenesis by encapsidating a virus RNA genome but also a non-structural role in HCV-induced pathogenesis by blocking innate immunity. Especially, it has been shown to regulate JAK-STAT signaling pathway through its direct interaction with Janus kinase (JAK) via its proline-rich JAK-binding motif ($^{79}{\underline{P}}GY{\underline{P}}WP^{84}$). However, little is known about the physiological significance of this HCV core-JAK association in the context of the virus life cycle. In order to gain an insight, a mutant HCV genome (J6/JFH1-79A82A) was constructed to express the mutant core with a defective JAK-binding motif ($^{79}{\underline{A}}GY{\underline{A}}WP^{84}$) using an HCV genotype 2a infectious clone (J6/JFH1). When this mutant HCV genome was introduced into hepatocarcinoma cells, it was found to be severely impaired in its ability to produce infectious viruses in spite of its robust RNA genome replication. Taken together, all these results suggest an essential requirement of HCV core-JAK protein interaction for efficient production of infectious viruses and the potential of using core-JAK blockers as a new anti-HCV therapy.

• Bulletin of the Korean Chemical Society
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• v.34 no.9
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• pp.2589-2593
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• 2013

Gene therapy using nonviral gene delivery carriers has focused on the development and modification of synthetic carriers such as liposomes and polymers. Most polymers that are commercially used are taking advantage of their polycationic character which allows not only strong ligand-DNA affinity but also competent cell penetration. Despite the relatively high transfection efficiencies, high cytotoxicity is continuously pointed out as one of the major shortcomings of polycationic polymers such as PEI. Studies on the utilization of peptides have therefore been carried out recently to overcome these problems. For these reasons, the human transcription factor Hph-1, which is currently known as a protein transduction domain (PTD), was investigated in this study to evaluate its potential as a gene delivery carrier. Although its transfection efficiency was about 10-fold lower than PEI, it displayed almost no cytotoxicity even at concentrations as high as $100{\mu}M$. Hph-1 was oxidatively polymerized to yield poly-Hph-1. The cell viability of poly-Hph-1 transfected U87MG and NIH-3T3 cells was almost as high as the control (untreated) groups, and the transfection efficiency was about 10-fold higher than PEI. This study serves as a preliminary evaluation of Hph-1 and encourages further investigation.

• Journal of Korean Medicine for Obesity Research
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• v.16 no.2
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• pp.109-115
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• 2016

Objectives: The all anti-obesity drugs currently approved by the US Food and Drug Administration work by reducing energy intake. In fact, no approved drug targets energy expenditure. In Korean medicine, it is known to Qi or Yang invigorating therapy could increase energy metabolism. Aconitum carmichaeli Debx (ACD) is a Yang invigorating herb, often used for treat obesity in Korean medicine. In the present study, the authors investigated the regulatory effects of ACD in energy metabolism and mitochondrial biogenesis in C2C12 skeletal muscle cells. Methods: The water extract of ACD (0.2, 0.5 and 1.0 mg/ml) were treated in differentiated C2C12 cells. The protein or mRNA levels of target genes were analyzed and mitochondrial mass were investigated. Results: ACD activated the expressions of peroxisome proliferator-activated receptor gamma coactivator 1-alpha ($PGC-1{\alpha}$), nuclear respiratory factor 1 and TFAM and increased mitochondrial mass. ACD also increased adenosin monophosphate-activated protein kinase (AMPK), and acetyl-CoA carboxylase. Conclusions: This study suggests that ACD has the potential to increase energy metabolism and mitochondrial biogenesis by activating AMPK and $PGC1{\alpha}$.

• Genomics & Informatics
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• v.12 no.2
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• pp.64-70
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• 2014

Human papillomavirus (HPV) infection is the leading cause of cancer mortality among women worldwide. The life-threatening infection caused by HPV demands the need for designing anticancerous drugs. In the recent years, different compounds from natural origins, such as carrageenan, curcumin, epigallocatechin gallate, indole-3-carbinol, jaceosidin, and withaferin, have been used as a hopeful source of anticancer therapy. These compounds have been shown to suppress HPV infection by different researchers. In the present study, we explored these natural inhibitors against E6 oncoprotein of high-risk HPV-16, which is known to inactivate the p53 tumor suppressor protein. A robust homology model of HPV-16 E6 was built to anticipate the interaction mechanism of E6 oncoprotein with natural inhibitory molecules using a structure-based drug designing approach. Docking analysis showed the interaction of these natural compounds with the p53-binding site of E6 protein residues 113-122 (CQKPLCPEEK) and helped the restoration of p53 functioning. Docking analysis, besides helping in silico validation of natural compounds, also helps understand molecular mechanisms of protein-ligand interactions.

• Archives of Pharmacal Research
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• v.29 no.11
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• pp.1018-1023
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• 2006

Chemoresistance remains the major obstacle to successful therapy of cancer. In order to understand the mechanism of multidrug resistance (MDR) that is frequently observed in lung cancer patients, here we studied the contribution of MDR-related proteins by establishing lung cancer cell lines with acquired resistance against etoposide. We found that human H460 lung cancer cells responded to etoposide more sensitively than A549 cells. Among MDR-related proteins, the expression of p-glycoprotein (Pgp) and lung resistance protein (LRP) were much higher in A549 cells compared with that in H460 cells. When we established H460-R1 and -R2 cell lines by progressive exposure of H460 cells to increasing doses of etoposide, the response against etopbside as well as doxorubicin was greatly reduced in R1 and R2 cells, suggesting MDR induction. Induction of MDR was not accompanied by a decrease in the intracellular accumulation of etoposide and the expression of MDR-related proteins that function as drug efflux pumps such as Pgp and MRP1 was not changed. We found that the acquired resistance paralleled an increased expression of LRP in H460 cells. Taken together, our data suggest the implicative role of LRP in mediating MDR in lung cancer.

• Journal of Life Science
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• v.14 no.5
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• pp.741-746
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• 2004

This study investigated the response of GLUT-4 and GRP-78 protein expression in soleus muscle of Streptozotocin-induced diabetic rats with caffeine oral administration by imposing different exercise intensities. Rats were randomly divided into 5 groups (n=6 in each group): diabetic group (D), diabetic-caffeine group (DC), diabetic-caffeine group with low intensity exercise (DCL), diabetic-caffeine group with moderate intensity exercise (DCM) and diabetic-caffeine group with high intensity exercise (DCH). The rats in DCL, DCM and DCH groups were exercised acutely by treadmill running for 8 meter/m, 16 meter/m and 25 meter/m, respectively. Little difference in GLUT-4 protein expression was shown in DC and DCL compared to D. GLUT-4 protein expression was decreased in DCM and increased in DCH was observed. GRP-78 protein expressions in DCL, DCM and DCH were little lower than that of D. An increase in GRP-78 protein was observed in DC. Improved insulin sensitivity with acute high intensity exercise gives the rats important therapy that lowers insulin requirement. This improvement of insulin sensitivity for glucose transport in skeletal muscle results from translocation of the GLUT-4 protein from the endoplasmic reticilum to the cell surface and increase in total quantity of GLUT-4 protein. It is not clear what mechanism reduced GRP-78 protein level in exercise group. It is merely conjectured that caffeine-induced lipolysis provided cells with energy in abundance and this relieved stress which cells are subjected to receive when performing exercise.

• 한국생물공학회:학술대회논문집
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• 2001.11a
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• pp.715-718
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• 2001

5-Aminolevulinic acid (ALA) can be used as a photodynamic herbicide / insecticide and also applied to photodynamic therapy for malignant skin tumor. In this study we developed recombinant E. coli system for the high productivity of ALA and for the on-line monitoring of fusion protein (EGFP::ALAS) by a fluorescence sensor.