11:10-12:00, Rm 103

Donghun AwardStem cell biology for developing Parkinson’s disease treatmentSang-Hun LeeDepartment of Biochemistry & Molecular Biology, College of Medicine, Hanyang University, Seoul133-791, KoreaStem cells with self-renewal and multi-developmental plasticity are the major type of cellsleading to tissue and organ development. Stem cells also reside in adult tissues and thetissue-specific stem cells participate in regenerative processes to repair the injured tissues asa response to toxic insults by undergoing proliferation, mobilization, and differentiation towardthe tissue cells. Thus facilitating the regenerative process is a strategy for curing intractabledegenerative disorders. Another therapeutic strategy, clinically proven in several diseases, isstem cell transplantation, which is designed to replace damaged tissues with new tissuedifferentiated from grafted stem cells. Parkinson’s disease (PD), characterized byprogressive degeneration of dopamine (DA) neurons in the midbrain, is a prime target forstem cell transplantation therapy. During the last decade, we have been undertaking stemcell research directed at the development of the therapy for neuro-degenerative disordersincluding PD. This presentation introduces our early research of midbrain-type DA neurondifferentiation from brain-derived stem cells, human ES and iPS cells, and cell transplantationapproaches utilized in experimental Parkinsonian animals using stem cells which have beenmanipulated to acquire DA neurogenic potentials. In the second part of this presentation, thecurrent state of stem cell transplantation in neural disorders is analyzed with attention toconcerns and roadblocks which hinder direct application in patients, and then our recentresearch to overcome these obstacles. Finally we will introduce mechanistic studies of neuralstem cell behaviors, aimed at developing therapies for CNS disorders by stimulatingendogenous brain stem cell-mediated regenerative processes.Chungsan AwardControl of adrenal steroidogenesis via H2O2-dependent, reversibleinactivation of peroxiredoxin III in mitochondriaSue Goo Rhee, In Sup Kil and Se Kyoung LeeDivision of Life and Pharmaceutical Sciences, Ewha Womans University, Seoul 120-750, KoreaCertain members of the peroxiredoxin (Prx) family undergo inactivation throughhyperoxidation of the catalytic cysteine to sulfinic acid during catalysis, and they arereactivated in an ATP-dependent manner by sulfiredoxin. We now show that PrxIII inmouse adrenal cortex is inactivated by H2O2 produced by cytochrome P450s duringsteroidogenesis stimulated by adrenocorticotropic hormone. This inactivation of PrxIIItriggers a sequence of events including the accumulation of H2O2, activation of p38mitogen-activated protein kinase, suppression of the synthesis of steroidogenic acuteregulatory protein, and inhibition of steroidogenesis. The levels of inactivated PrxIII,activated p38, and sulfiredoxin undergo circadian oscillations. Steroidogenic tissuespecificablation of sulfiredoxin in mice resulted in the persistent accumulation of inactivePrxIII and oxidative damage to the adrenal gland. The seeming imperfections of electronleakage by cytochrome P450s and inactivation of PrxIII by its own substrate thus appearto represent an evolutionary adaptation for feedback inhibition of steroidogenesis.Macrogen Women Scientist AwardMolecular pathogenesis of Alzheimer’s diseaseInhee Mook-JungDepartment of Biochemistry and Biomedical Sciences, Seoul National University College ofMedicine, Seoul, KoreaAlzheimer’s disease is age-related neurological disorder and cognitive impairment is themajor symptom of AD. Abnormal production and/or clearance of misfolded proteins mayaccumulate and form amyloid deposition in the brain. Many of biochemical and transgenicanimal models studies have provided strong support to the concept that amyloid fibrilsplayed essential roles in amyloid pathogenesis. However, many recent studies report thetissue specific accumulation of soluble Aβoligomers and their various effect on cell.These findings led to a new view that soluble Aβoligomers may be crucial role in ADpathogenesis. Here, recent findings about role of soluble Aβoligomers will be discussedin the pathogenesis of Alzheimer’s disease. Possible therapeutic approaches aimed atlowering oligomer toxicity are also considered. Understanding of the mechanisms inducedby Aβoligomers may lead to the development of effective treatments for AD.Merck Young Scientist Award 1stGalectin-3 increases gastric cancer cell motility by up-regulating fascin-1expressionSeok-Jun Kim, Il-Ju Choi, Teak-Chin Cheong, Sang-Jin Lee, Reuben Lotan, SeokHee Park and Kyung-Hee ChunGastric cancer branch, Division of translational & clinical research I, National Cancer Center,Goyang, KoreaGalectin-3 is a β-galactoside-binding protein that increases gastric cancer cell motility andis highly expressed in gastric tumor cells. Also, Galectin-3 increase cell motility, but themechanisms of this process are not understood. Therefore, we investigated that silencedgalectin-3 expression in AGS cell lines using siRNA and determined the effects on fascin-1, as an actin-bundling protein, expression and cell motility. As a result, we demonstratethat malignant gastric tissues expressed high levels of galectin-3 and fascin-1, comparedwith normal tissues. Silencing of galectin-3 reduced fascin-1 expression and decreasedcell motility. Galectin-3 overexpression reversed these effects. Silencing of fascin-1 alsoreduced cell motility. Furthermore, galectin-3 silencing inhibited the interaction betweenGSK-3β, β-catenin, and TCF-4, and the binding of β-catenin/TCF-4 to the fascin-1promoter. Nuclear localization of GSK-3βand β-catenin were not detected when galectin-3 was silenced. Overexpression of mutated galectin-3 (with mutations in the GSK-3βbinding and phosphorylation motifs) did not increase fascin-1 levels, in contrast tooverexpression of wild-type galectin-3. Taken together, we propose that galectin-3increases cell motility by up-regulating fascin-1 expression.Dongchun AwardParacrine functions of mesenchymal stem cells in the tumormicroenvironmentJae Ho KimPusan National University School of Medicine, Pusan, KoreaMesenchymal stem cells stimulate tumor growth in vivo through a lysophosphatidic acid(LPA)-dependent mechanism. However, the molecular mechanism by whichmesenchymal stem cells stimulate tumorigenesis is largely elusive. In the present study,we demonstrate that conditioned medium from A549 human lung adenocarcinoma cells(A549 CM) induces expression of periostin, an extracellular matrix protein, in humanadipose tissue-derived mesenchymal stem cells (hASCs) through LPA-dependentmechanism. Using a xenograft transplantation model of A549 cells, we demonstrated thatco-injection of hASCs potentiated tumor growth of A549 cells in vivo and that cotransplantedhASCs expressed not only periostin but also α-smooth muscle actin (α-SMA), a marker of carcinoma-associated fibroblasts. Short hairpin RNA-mediatedsilencing of periostin resulted in blockade of hASC-stimulated growth of A549 xenografttumors and in vivo differentiation of transplanted hASCs to carcinoma-associatedfibroblasts. Conditioned medium derived from LPA-treated hASCs (LPA CM) potentiatedproliferation and adhesion of A549 cells and short interfering RNA-mediated silencing orimmunodepletion of periostin from LPA CM abrogated proliferation and adhesion of A549cells. These results suggest a pivotal role for hASC-secreted periostin in the tumormicroenvironment.Merck Young Scientist Award 2ndStructures of ClpP in complex with ADEP antibiotics reveal its activationmechanismByung-Gil LeeSchool of Life Sciences and Biotechnology, Korea University, Seoul, KoreaClp-family proteins are prototypes for studying the mechanism of ATP-dependentproteases because the proteolytic activity of the ClpP core is tightly regulated byactivating Clp-ATPases. Nonetheless, the proteolytic activation mechanism has remainedelusive because of the lack of a complex structure. ADEPs (acyldepsipeptides), arecently discovered class of antibiotics, activate and disregulate ClpP. Here we haveelucidated the structural changes underlying the ClpP activation process by ADEPs. Wepresent the structures of Bacillus subtilis ClpP alone and in complex with ADEP1 andADEP2. The structures show the closed-to-open-gate transition of the ClpP N-terminalsegments upon activation as well as conformational changes restricted to the upperportion of ClpP. The direction of the conformational movement and the hydrophobicclustering that stabilizes the closed structure are markedly different from those of otherATP-dependent proteases, providing unprecedented insights into the activation of ClpP.68 Korean Society for Biochemistry and Molecular Biology