11:10-12:00, Rm 103

Cell: differentiation, division and deathC-17-64Exposure of PC12 cells to extremely low frequency electromagnetic fieldpotentiates NGF-Mediated neuronal differentiationJin-Han Shim, Geon Go, Madhumita Patel and Jung-Suk Sung*Department of Life science, Dongguk University-Seoul, Seoul 100-715, KoreaHuman beings are constantly exposed to diverse electromagnetic fields (EMFs) Adverseeffects of high-frequency EMFs such as IR and UV on human health are well defined,whereas biological effect of low-frequency EMFs has not been understood. This studyaimed to evaluate effects of the exposure of 50 Hz low-frequency EMF on NGF-mediatedneuronal differentiation of PC12 cells. The number of differentiated PC12 cells wasremarkably increased when co-treated cells with nerve growth factor (NGF) and 50 HzEMF compared to the cells only treated NGF. The mRNA expression of the genesinvolving neuronal differentiation, Tubb3 and Map2, was up-regulated by the exposure toEMF. Protein expression of neuronal specific markers and neurite formation in PC12 cellswere also stimulated by 50 Hz-EMF exposure. Accordingly, the protein level of NGFreceptor, TrkA, and its phosphorylation were increased by EMF exposure. Overall resultssuggested that extremely low-frequency EMF potentiates and intensifies NGF-mediatedneuronal differentiation. [This work was supported by the Pioneer Research CenterProgram (2009-0082965)].C-17-67Neutrophil lactoferrin controls cell growth by activating apoptotic signalpathway in heLa cell lineHae Seong Jeong and Sang-Yun ChoiSchool of Life Sciences and Biotechnology, Korea University, Seoul 136-701, KoreaLactoferrin (Lf) is an iron binding glycoprotein, and involved in the regulation of cellproliferation and apoptosis in a variety of mammalian cells. The level of circulating Lfmight be important for the growth control of cells. It has been proposed that the level of Lfin a local area might be a critical determinant for the cell death and proliferation.Especially, Lf is believed to have a role in immune system and thought to be implicatedwith the regulation of tumor cell growth. In this study, it was investigated whether Lf caninduce apoptosis and whether it might be associated with a caspase signaling pathway inHeLa cells. Treatment of HeLa with Lf at a low concentration increased cell viability, andinduced the inactivation of caspase 9. On the other hand, a relatively high level of Lfdecreased cell viability, and induced the activation of caspase 3, 8, and 9, as evaluatedby levels of cleaved caspases. In addition to the circulating Lf, our studies also designedto monitor the distribution of Lf around solid tumor tissue in vivo usingimmunohistochemistry method. Collectively, our studies demonstrate that Lf functions asa biological mediator of apoptosis in the Hela cells via the caspase signaling pathway.C-17-65Effects of Yuza extract and citrus fruit flavonoid hesperetin onUVA/UVC irradiation mediated damages of human keratinocyte HaCaTcellsHuiyun Hwang and Jung-Suk SungDepartment of Life Science, Dongguk University-Seoul, Seoul 100-715, KoreaYuza, a Korean citrus fruit is full of polyphenols and limonoids which have been reportedas a candidate for protection of human skin from oxidative stress. The major citrusflavonoid hesperidin is one of the most abundant natural flavonoids, and on ingestion itreleases its aglycone, i.e, hesperetin. The present study aimed to determine the UVA andUVC protective effects and molecular mechanisms of Yuza and its major compoundhesperetin against UV-induced cellular damages in cultured human keratinocyte HaCaTcells. Yuza fruit juice extract showed antioxidant properties and attenuated cell deathafter UVA irradiation, suggesting that the extract was involved in the prevention of UVAinducedoxidative damages. Treatment of hesperetin with UV irradiated cells modulatedmitogen activated protein kinases (MAPKs) signaling pathways. Proteomic analysisrevealed that Yuza and hesperetin regulate levels of several proteins to protect the cellsfrom UV damages. Taken together, we suggest that Yuza extracts and hesperetin can beapplied to be effective substances in cosmetics against UV irradiation and oxidativestress. This work was supported by technology development program of Ministry forFood, Agriculture, Forestry and Fisheries, Korea (iPET-20083061).C-17-68Activated protein C enhances adipocyte differentiation and adiponectinexpression in 3T3-L1 cellsMyung-Hee Moon, Jae-Kyo Jeong, You-Jin Lee, Jeong-Yun Choi, Yang-Gyu Park,Pyung-On Kim, Bum-Chul Bae, Jae-Won Seol and Sang-Youel ParkKorea Zoonoses Research Institute, Center for Healthcare Technology Development, College ofVeterinary Medicine, Chonbuk National University, Jeonju 561-756, KoreaAdipocyte dysfunction is strongly associated with the development of cardiovascular riskfactors and diabetes. It is accepted that the regulation of adipogenesis or adipokinesexpression, notably adiponectin, is able to prevent these disorders. In this report, weshow that activated protein C (APC), a serine protease enhances 3T3-L1 adipocytedifferentiation as evidenced by increased triglyceride accumulation. At a molecular level,mRNA expression levels of both PPARγand C/EBPα, the master adipogenic transcriptionfactors, are markedly increased by APC. Moreover, mRNA levels of PPARγtarget genessuch as LPL, aP2 and adiponectin are up-regulated by APC. We also show that APCenhances the expression and secretion of adiponectin. Taken together, these resultssuggest that APC may be beneficial for reducing insulin resistance through its potency toregulate adipocyte differentiation and function.C-17-66Cyclin-dependent kinase 4 acts as a molecular switch to transdifferentiatehuman mesenchymal stem cells into neural cellsJanet Lee and Chang-Woo LeeDepartment of Molecular Cell Biology, Sungkyunkwan University School of Medicine, Suwon440-746, KoreaMulti-potent mesenchymal stem cells (MSCs) are capable of differentiating into a varietyof cell types from different germ layers. However, the molecular and biochemicalmechanisms underlying the trans-differentiation of MSCs into specific cell types remain tobe elucidated. In this study, we unexpectedly found that treatment of human MSCs withcyclin-dependent kinase (CDK) inhibitor, in particular CDK4 inhibitor, selectively leads totrans-differentiation into neural cells (primarily glial cells) with a high frequency.Specifically, targeted inhibition of CDK4 expression using a recombinant adenovialshRNA induces the neural glia trans-differentiation of human MSCs. Importantly, theforced regulation of CDK4 activity showed reciprocal reversibility between neural gliadifferentiation and dedifferentiation of human MSCs. Together, these results may providenovel molecular evidence underlying the neural glia trans-differentiation of human MSCs,and CDK4 signaling appears to act as a molecular switch between the reversible neuralglia differentiation and dedifferentiation of human MSCs.C-17-69Sphingosine-1-phosphate promotes human osteoblast differentiationthrough PI3K pathwayMyung-Hee Moon, Jae-Kyo Jeong, You-Jin Lee, Jeong-Yun Choi, Yang-Gyu Park,Pyung-On Kim, Bum-Chul Bae, Jae-Won Seol and Sang-Youel ParkKorea Zoonoses Research Institute, Center for Healthcare Technology Development, College ofVeterinary Medicine, Chonbuk National University, Jeonju 561-756, KoreaThe survival of osteoblasts is one of the determinants of the development ofosteoporosis. The naturally occurring phospholipids sphingosine-1-phosphate (S1P)strongly involved in the regulation of cell growth and differentiation. we investigated theosteoblastic differentiation induced by S1P in osteoblastic cell line hFOB. Osteoblasticdifferentiation was determined by assaying alkaline phosphatase (ALP) activity andmineralization degree. Expression of Runt-related transcription factor 2 (Runx2),osteocalcin and collagen type 1 was assessed by Real-time RT-PCR. AKT (PKB) andextracellular signal-regulated kinase (ERK) 1/2 was assessed by immunoblot. S1P hadan effect on osteoblastic differentiation by means of ALP activity, Runx2, osteocalcin andtype 1 collagen upregulation. Induction of differentiation by S1P was associated withstrongly increased AKT and weakly ERK 1/2 via S1P receptor 1 (S1P1). SEW2871,S1P1 selective agonist, induced osteoblast differentiation and W146, S1P1 antagonist,blocked the osteoblastic differentiation effect of S1P. In this study, we showed that S1Pinduced osteoblastic differentiation through the S1P1-PI3K-AKT-Runx2 pathways andthat is a promising agent for treating osteoporosis.210 Korean Society for Biochemistry and Molecular Biology