11:10-12:00, Rm 103

Bioinformatics and systems biologyA-17-01Telomerase activity modulates the Bcl-2 dependent-apoptosis of thehuman brain tumorsChoong-Hyun Kim, Jae-Min Kim, Jin-Hwan CheongDepartment of Neurosurgery, Hanyang University Guri Hospital, Guri 471-701, KoreaThe regulation of apoptosis is influenced by various gene products including Bcl-2, whichhas been known to be anti-apoptotic property. In addition, telomerase, aribonucleoprotein that synthesizes telomeres, has been detected in many humanneoplasms. In the current study, we examined the apoptotic effect by Bcl-2 expressionand telomerase activity in the human brain tumors. A total of 76 cases of surgicallyresected brain tumors were studied. Telomerase activity was detected by the telomericrepeat amplication protocol assay (TRAP) and Bcl-2 protein was examined by theWestern blot analysis. Apoptosis of the specimens was also detected by DNAfragmentation analysis. Telomerase activity was detected in 65.8% (50 of 76) of the braintumors, which induced apoptosis in 20.0% (10 of 50). Bcl-2 was also expressed in 23.7%(18 of 76) of the brain tumors, which induced apoptosis in 11.1% (2 of 18). In 14 caseswith Bcl-2 expression and negative telomerase activity, apoptosis was detected in 21.4%(3 of 14). However, apoptosis was not induced in all 4 cases with Bcl-2 expression andtelomerase activity. These indicated that apoptosis was enhanced in the brain tumorswith Bcl-2 expression and negative telomerase activity (p < 0.05). In the 24 cases withoutBcl-2 expression and telomerase activity, detection rate of apoptosis was 25% (6 of 24).Apoptosis was induced in 23.4% (8 of 34) of brain tumors, which Bcl-2 was not expressedand telomerase activity was positive. Their difference was not significant statistically. Ourresults suggest that apoptosis may be modulated by telomerase activity of the humanbrain tumors having Bcl-2 expression. However, telomerase activity may not affect onapoptosis of the brain tumors without Bcl-2 expression.A-17-02APE1/Ref-1 promotes the effect of agiotensin II on Ca2+-activated K+channel in human endothelial cells via suppression of NADPH oxidaseWon Sun ParkDepartment of Physiology, Kangwon National University School of Medicine, Chuncheon, KoreaThe effects of angiotensin II (Ang II) on whole-cell large conductance Ca2+-activated K+(BKCa) currents was investigated in control and Apurinic/apyrimidinicendonuclease1/redox factor 1 (APE1/Ref-1)-overexpressing human umbilical veinendothelial cells (HUVECs). Ang II blocked the BKCa current in a dose-dependentfashion, and this inhibition was greater in APE1/Ref-1-overexpressing HUVECs than incontrol HUVECs. Pretreatment with the NADPH oxidase inhibitor diphenyleneiodonium(DPI) or knock down of NADPH oxidase (p22 phox) using siRNA increased the inhibitoryeffect of Ang II on the BKCa currents, similar to the effect of APE1/Ref-1 overexpression.In addition, application of Ang II increased the superoxide and hydrogen peroxide levelsin the control HUVECs but not in APE1/Ref-1-overexpressing HUVECs. Furthermore,direct application of hydrogen peroxide increased BKCa channel activity. Finally, theinhibitory effect of Ang II on the BKCa current was blocked by an antagonist of the Ang IItype 1 (AT1) receptor in both control and APE1/Ref-1-overexpressing HUVECs. Fromthese results, we conclude that the inhibitory effect of Ang II on BKCa channel function isNADPH oxidase-dependent and may be promoted by APE1/Ref-1.A-17-03Down-regulation of CYP1A1 expression by environmental toxicants inhypomethylated cellsYoungchul Lim¹, Yoonjung Kim², Eunil Lee¹ , ² , ³¹Department of Preventive Medicine & Medical Research Center for Environmental Toxico-Genomics and Proteomics, Korea University, Seoul 136-705, Korea, ²Department of Public Health,Korea University, College of Medicine, Graduate School of Medicine, Seoul 136-705, Korea,³Department of Preventive Medicine, Korea University, College of Medicine, Seoul 136-705, KoreaProtein arginine methylation is one of the posttranslational modifications, catalyzed byprotein arginine methyltransferases (PRMTs) with S-adenosyl-l-methioinine (SAM) as themethyl donor. PRMTs produce monomethyl and dimethyl (asymmetric or symmetric)arginines in proteins. Previously, PRMT1 and PRMT4/CARM1 was shown to function astranscriptional coactivators for nuclear receptors and many other transcription facotrs, atleast in part through histone methylation. The aryl hydrocarbon receptor (AhR) is a helixloop-helixtranscription factor activated by endogenous ligands and xenobiotics such asthe environmental contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) orbenzo[a]pyrene (BP). In the present study, we investigated the interrelationship betweenprotein arginine methylation and CYP1A1 gene expression by TCDD or BP. When thecells were maintain at hypomethylated state by the treatment of adenosine dialdehyde(AdOx), a transmethylation inhibitor, CYP1A1 expression by TCDD was significantlydown-regulated compared to untreated control cells. In addition, when the cells weretreated by BP in a time-dependent manner, hypomethylated cells also showed delayedand reduced CYP1A1 expression. However, AhR expression in hypomethylated cellsshowed no significant change compar.A-17-04Bladder tumor-targeting peptide-mediated anti-tumor activity of a proapoptoticpeptideHyun-Kyung Jung, Mi-Kyung Kwak, Eun-Ju Lee, Rang-Woon Park, In-San Kim,Byung-Heon LeeDepartment of Biochemistry and Cell Biology, School of Medicine, Kyungpook NationalUniversity, Daegu, KoreaBladder carcinoma is the most common urothelial malignancy in developed countries andthe rate of recurrence is pretty high. Using phage display, we have previously identified abladder tumor-targeting peptide with the amino acid sequence of CSNRDARRC (namely,Bld-1). Bld-1 was shown to target bladder tumor in carcinogen-induced tumor-bearingrats. A synthetic pro-apoptotic peptide KLAKLAKKLAKLAK, called (KLAKLAK)2, hasbeen demonstrated to induce apoptotic cell death of tumor cells. In this study, we usedBld-1 as a homing domain to help the pro-apoptotic peptide selectively bind to bladdertumor cells and allow its internalization. Bld-1 preferentially bound to HT-1376 bladdertumor cells, while little binding to A549 lung tumor cells was observed. Confocalmicroscopic analysis demonstrated that Bld-1 was efficiently internalized into HT-1376cells. Bld-1-conjugated D-enantiomer D(KLAKLAK)2 was synthesized and incubated withHT-1376 cells for 24, 48, and 72 h. Bld-1- D(KLAKLAK)2 exerted its cytotoxic activity onHT-1376 cells in a dose- and time-dependent manner. In addition, D(KLAKLAK)2 alonealso showed cytotoxic activity after 48 h treatment but this was in a lesser extent ascompared to Bld-1-D(KLAKLAK)2. The cell death induced by Bld-1-D(KLAKLAK)2 wasdue to apoptosis as shown by annexin V and propidium iodide staining. Bld-1-D(KLAKLAK)2 more efficiently inhibited tumor growth in HT-1376 bladder tumor-bearingmice than D(KLAKLAK)2. These results suggest that Bld-1-D(KLAKLAK)2 might be auseful therapeutic agent for targeted therapy of bladder tumor.A-17-06Tension force stimulates type I Collagen and MMP-1 expression inHuman Periodontal Ligament Fibroblasts through activation of MAPK-AP-1/NF-κB signalingSung-Ho Kook¹, Shin-Saeng Lim², Young-Mi Jeon², Jong-Ghee Kim², Seung-YoupLee², Jeong-Chae Lee²¹Division of Hematology & Oncology, Department of Medicine, University of Pittsburgh CancerInstitute, Pittsburgh, PA 15232, USA, ²Institute of Oral Biosciences and School of Dentistry(BK21 Program), Research Center of Bioactive Materials, Chonbuk National University, Jeonju561-756, KoreaExpression of Type I collagen (COL I) and matrix metalloproteinase-1 (MMP-1) in PDLfibroblasts (PLF) is sensitive to physiological and mechanical stresses and this is criticalfor PDL remodeling accompanied by alveolar bone remodeling. In this study, weinvestigated how dose tension force regulates the expression of COL I and MMP-1 andexplored the possible roles of mitogen-activated protein kinases (MAPKs) andtranscription factors such as activator protein-1 (AP-1) and nuclear factor-kappaB (NF-κB). Tension force stimulated mRNA expression of COL I and MMP-1 in the cells and alsoactivated MAPKs including extracellular signal-regulated kinase (ERK), c-Jun N-terminalkinase (JNK), and p38 MAPK. Knockdown of c-Jun by transfecting the cells with itsantisense oligonucleotides diminished the force-induced increase of the matrix geneexpression. Especially, ERK inhibitor but not JNK or p38 MAPK inhibitor attenuated theforce-mediated stimulation of NF-κB-DNA binding and MMP-1 expression. Collectively,the present results provides mechanotransduction pathways involved in matrix geneexpression in PLF, where tension force-stimulated expression of COL I and MMP-1 iscontrolled by ERK/JNK-AP-1 and ERK-NF-κB signaling pathways.A-17-07Comparative study of genetic variations of the VP1 gene of foot-andmouthdisease virus (serotype O) between Korean and other countriesisolatesInsung Ahn, Se-Eun Bae¹and Hyeon Seok Son¹ , ²Supercomputing Center, Korea Institute of Science and Technology Information, 335, Gwahangno,Yuseong-Gu, Daejon 305-806, Korea, ¹Interdisciplinary Graduate Program in Bioinformatics,College of Natural Science, Seoul National University, 599 Gwanak-Ro, Gwanak-Gu, Seoul 151-742, Korea, ²Laboratory of Computational Biology & Bioinformatics, Institute of Health andEnvironment, Graduate School of Public Health, Seoul National University, 599 Gwanak-Ro,Gwanak-Gu, Seoul 151-742, KoreaIn this study, we compared all the genetic variations of the VP1 gene of foot-and-mouthdisease viruses (FMDVs) according to their isolated regions since 2000. We analyzed theRSCU values as well as the phylogenetic relationships among geographical regions, andthen, calculated the genetic substitution patterns between Korean and other countryisolates in codon-basis. For more intensive analysis, we also computed the ratio of exactmatching codons in synonymous groups (EMC) as well as the ratio of synonymouscodon substitutions (SCS) in all amino acid groups. Here, we observed that GCcomposition of FMDVs in the third codon position was strictly conserved while SCS andEMC values became decreased. Although, there was less variation among amino acidswhen we calculate SCS values between Korean and other country isolates, there weredynamic differences in EMC values among synonymous codon groups as well asgeographical regions. The EMC values of 4- and 6-fold degenerate amino acids showedsignificantly low values while most of 2-fold degenerate amino acids showed nosignificant differences. Our finding suggested that the different EMC patterns amongamino acids might be a determining factor for the direction of evolutions in FMDV.160 Korean Society for Biochemistry and Molecular Biology