11:10-12:00, Rm 103

Metabolism and metabolic diseasesP-18-01Induction of Heme oxygenase-1 by Korean red ginseng water extract as acytoprotective effect in human endothelial cellsHana Yang, Seung-Eun Lee, Sung-Il Jung, Yong-Seek Park*Department of Microbiology, School of Medicine, Kyung Hee University, #1 Hoegi-dong,Dongdaemun-gu, Seoul 130-701, KoreaKorean red ginseng (KRG) is one of the most popular herbal medicines, which has beenemployed for several vascular diseases, such as atherosclerosis, diabetes, andhypertension. However, the fundamental protective mechanism of KRG in cardiovasculardiseases is not clearly understood. In the present study, we demonstrate that KRG waterextract induces a cytoprotective protein, HO-1 in human umbilical vein endothelial cells(HUVECs). Our data indicates Nrf2 involvement and cytoprotective effect of HO-1 againstoxidative stress on HUVECs. This study provides biological evidence in support of theuse of KRG in the treatment of stroke, hypertension, and atherosclerosis.P-18-04Distinctive role of Akt1/PKBαin phenotypic modulation of vascularsmooth muscle cellsSung Ji Yun, Eun Kyoung Kim, Jung Min Ha, Young Hwan Kim, In Hye Jin, DaeHan Woo, Hye Sun Lee, Chi Dae Kim and Sun Sik BaeMRC for Ischemic Tissue Regeneration and Department of Pharmacology, College of Medicine,Pusan National University, Yangsan 626-770, KoreaUnder normal culture conditions, rat aortic smooth muscle cells (RASMCs) display theirphenotypic modulation from a dedifferentiated (synthetic type) to a differentiated(contractile type) state. Insulin-like growth factor 1 (IGF-1) is unique among growth factorsin promoting RASMCs differentiation via preferential activation of phosphatidylinositol 3-kinase (PI3K) pathways. The differentiation of synthetic type RASMC is achieved byrepetitive subculture at high cell density. Especially, plating the cells on fibronectin-coateddish enhanced the differentiation of RASMCs. Both Akt and ERK were significantlyactivated by fibronectin. Inhibition of PI3K/Akt signaling pathways blocked thedifferentiation of RASMC. More importantly, silencing of Akt1 abolished the differentiationof RASMCs. Moreover, silencing of integrin-linked kinase (ILK) completely blocked thedifferentiation of RASMCs, and reduced the phosphorylation of Akt. In addition, Silencingof Akt1 impaired promoter activity of smooth muscle cell marker genes. Finally, micelacking Akt1 displayed enhanced neointima formation after carotid artery ligation. Giventhese results, we suggest that Akt1 is involved in extracellular matrix associated signalingpathways and regulates vascular integrity to contractile phenotype.P-18-02Inhibition of stearoyl-CoA desaturase 1 activates AMPK and enhancesbeneficial lipid metabolic effects in vitroEunha Kim, Jung-Han Lee, Chang-Kee HyunSchool of Life Science, Handong Global University, Pohang, Kyungbuk 791-708, KoreaSCD1 whole body deficiency protects mice from diet-induced obesity. To understand thetissue-specific role of SCD1 in energy homeostasis, we investigated the responses ofadipocytes, hepatocytes and myotubes to SCD1 inhibition. 3T3-L1 treated with a SCD1inhibitor showed a decrease in expression of lipogenic genes such as FAS, ACC andSREBP1c but no change in expression of FA oxidative genes including CPT1, UCP2,and PGC1-α. SCD1 inhibitor-treated mouse primary hepatocytes showed an increase inexpression of FA oxidative genes AOX, CPT1, and PGC1-α. SCD1 inhibitor-treatedC2C12 showed a decrease in FAS expression and an increase CPT1 expression. AMPKis known to regulate cellular metabolism in response to available energy and AMPKactivation is associated with an increase of FA oxidation and a decrease of lipogenesis. Inour cell systems, when SCD1 was inhibited, AMPK phosphorylation was increased in allof adipocytes, hepatocytes and myotubes. Together, these results indicate that inhibitionof SCD1 activity has beneficial lipid metabolic effects of increased FA oxidation anddecreased lipogenesis, which is at least in part due to an increase of AMPK. [Supportedby the National Research Foundation Grant funded by the Korean Government (MEST,2009-0065952)]P-18-05APH-6E, a novel amorphastilbol derivative, enhances adipocytedifferentiation in 3T3-L1 preadipocytes and human bone marrowmesenchymal stem cells through PPAR-gamma transactivationWoojung Lee, Jungyeob Ham, Yong Kee Kim¹and Su Nam KimKIST Gangneung Institute, Gangneung 210-340 and ¹Department of Pharmacology, KwandongUniversity College of Medicine, 522 Naegok-dong, Gangneung-si, Gangwon-do 210-701, KoreaPeroxisome Proliferator Activated Receptor Gamma (PPAR-gamma) is a liganddependenttranscriptional factor that belongs to the nuclear hormone receptor superfamilyand forms a heterodimer with a retinoid X receptor. It has been known that PPAR-gammaplays a key role in adipocyte differentiation and insulin sensitivity.In this study, we showthat APH-6E, a novel amorphastilbol derivative, leads to adipocyte differentiation throughthe transactivation of PPAR-gamma and enhanced accumulation of triglyceride in 3T3-L1and human bone marrow mesenchymal stem cells (hBM-MSCs). APH-6E also stronglyinduced luciferase activity than APH on human PPAR-gamma and directly bind to PPARgammaLBD. We suggested that APH-6E, amorphastilbol derivative, is a novel agonist ofPPAR-gamma and may be beneficial for reducing insulin resistance through its potencyto regulate adipocyte differentiation.P-18-03Cytochrome P450 4A regulates endoplasmic reticulum stress-inducedhepatic insulin resistance and apoptosis in type 2 diabetesEdmond Changkyun Park, Dong-gyu Lee, Yeonhee Hong, Gun-Hwa Kim*Division of Life Science, Korea Basic Science Institute, 52 Eoeun-dong, Yusung-gu, Daejeon 305-333, KoreaER stress is known to be implicated in the development of type 2 diabetes (T2DM). Underdiabetic conditions, ER stress is induced and the JNK pathway is subsequently activated,which is involved in insulin resistance and apoptosis. However, the underlyingmechanisms that regulate ER stress and T2DM are poorly understood. Here we showthat drug metabolic protein CYP4A is essential regulates the ER stress-induced insulinresistance and apoptosis in the diabetic mouse liver. Through the extensive comparisonof protein profile between normal and diabetic mice liver by mass spectrometry, we foundthat CYP4A is upregulated in db/db diabetic mice. In db/db mice, ectopic induction ofCYP4A caused ER stress and insulin resistance. In contrast, inhibition of CYP4A activityreduced the ER stress, insulin resistance and apoptosis. Moreover, inactivation of CYP4Aimproved the diabetic physiological phenomena, such as hepatic steatosis and glucosetolerance. In addition, CYP4A regulated the lipid peroxidation and lipogenesis, which areknown to be a cause of ER stress. These data demonstrate that CYP4A is an importantregulator of ER stress-induced insulin resistance and apoptosis and that the regulation ofCYP4A function could be a therapeutic target against T2DM and metabolic syndrome.P-18-06Over expressed CBR1 attenuates pancreatic β-cell apoptosis throughinhibition of ROS generation in glucolipotoxic conditionAmarjargal Dashdorj, M.A. Rashid and Sung Soo KimDepartment of Biochemistry and Molecular Biology, Medical Research Center for Bioreaction toReactive Oxygen Species and Biomedical Science Institute, School of Medicine, Kyung HeeUniversity, Seoul 130-701, KoreaCarbonyl reductase 1 (CBR1) may play an important role as an oxidation-reductioncatalyst in biological process. Oxidative stress has been implicated in the pathogenesis ofpancreatic β-cell failure of type 2 diabetes.CBR1 expression and enzyme activity levelswere significantly decreased in pancreatic islets isolated from db/ab mice. Overexpression of CBR1 significantly increased cell survival rates, decreased levels oflipogenic enzymes, lipid per oxidation, and suppresses ROS accumulation and ERstress, nuclear active form of SREBP 1c and also increases glucose stimulated insulinsecretion in pancreatic β-cells. Our research suggests that CBR1 might be one of themajor factor involving pancreatic β-cell failure in type 2 diabetes patients.314 Korean Society for Biochemistry and Molecular Biology