11:10-12:00, Rm 103

OthersU-18-49AIP2, one of AROS interacting proteins, associates and regulates SIRT1functionMino Moon and Eun Joo KimBK21 Graduate Program, Department of Molecular Biology, Dankook University, Yongin-si,Gyeonggi-do 448-701, KoreaSIRT1, the best characterized mammalian homolog of yeast SIR2, is involved inchromatin remodeling, which culminates in gene silencing, the DNA damage response,and an extended lifespan following caloric restriction. Recently, we found that AROS(Active Regulator of SIRT1), which cooperates with SIRT1 and facilitates suppression ofp53 activity. To understand the molecular mechanism underlying SIRT1 regulation byAROS, we performed yeast two-hybrid screen and isolated several clones. One identifiedclone, called AIP2 (AROS interacting protein 2), could interact with AROS through the C-terminal region. Such interaction was further confirmed by GST pull-down assay in vitroand immunoprecipitation and fluorescence microscopy in vivo. In addition, AIP2 couldassociate with SIRT1 as determined by immunoprecipitation and fluorescencemicroscopy. GST-pull down assay showed no direct interaction between AIP2 andSIRT1. Furthermore, the AROS binding-null SIRT1 mutant was also defective ininteraction with AIP2. Taken together, these data suggest that AIP2 associates withSIRT1 via AROS. The physiological significance of the interaction is currently beinginvestigated.U-18-52Maternal exposure to fenarimol promotes reproductive performance inmouse offspringMira Park¹, Jiyou Han¹, Jeong-Jae Ko², Woo-Sik Lee³, Tae Ki Yoon³, KangseokLee⁴and Jeehyeon Bae¹ , *¹Department of Pharmacy & ²Biomedical Science, CHA University, Seongnam 463-836, Korea,³Fertility Center of CHA Gangnam Medical Center, Seoul 135-081, Korea, ⁴Department of LifeScience, College of Natural Science, Chung-Ang University, Seoul 156-756, KoreaAlthough fenarimol is a widely used chlorinated fungicide, transgenerational studies oflow doses of fenarimol exposure are not currently available. Pregnant mice were orallyexposed to low doses (0, 2, 20, and 200 µg/kg body weight) of fenarimol duringgestational and lactational periods. Fenarimol-exposed F1 mice had shortened AGDs,increased body weight, increased number of pups, increased number of ovarian follicles,and enhanced sperm quality. Microarray data showed 82 upregulated and 743downregulated genes in the ovaries of fenarimol-exposed mice. In addition, Nobox, apivotal gene required for proper folliculogenesis, was significantly increased in the ovariesof F1 mice. In conclusion, maternal exposure to fenarimol promotes normal reproductivefunction in female mouse offspring by increasing the expression levels of genes crucialfor ovarian folliculogenesis, identifying fenarimol as a chemical that stimulatesreproductive performance. This work was supported by the Priority Research CentersProgram (2009-0093821) through the National Research Foundation of Korea (NRF) ofthe Ministry of Education, Science and Technology and by a grant (A084923) from theKorea Healthcare Technology R&D Project from the Ministry of Health, Welfare andFamily Affairs.U-18-50Maternal exposure to simazine disturbs reproductive performance inmale mouse offspringHo-Oak Park¹, Mira Park¹, Jeong-Jae Ko², Woo-Sik Lee³, Tae Ki Yoon³, KangseokLee⁴and Jeehyeon Bae¹ , *¹Department of Pharmacy & ²Biomedical Science, CHA University, Seongnam 463-836, Korea,³Fertility Center of CHA Gangnam Medical Center, Seoul 135-081, Korea, ⁴Department of LifeScience, College of Natural Science, Chung-Ang University, Seoul 156-756, KoreaSimazine known as a potent endocrine disruptor in wildlife and laboratory animals is atriazine herbicide that has been applied worldwide for agriculture. In this study, pregnantmice were orally exposed to low doses of simazine during gestational and lactationalperiods, and their male offspring were assessed. Simazine-exposed mice showed thedecreased body weight, testis weight and sperm quality. In addition, apoptosis wereinduced in the testes of F1 mice maternally exposed to simazine. Differentially expressedgenes in F1 testis maternally exposed to simazine were identified by DNA microarray,and showed 775 upregulated and 791 downregulated genes. Specially, we found thattesticular relaxin pathway was affected in the offspring upon maternal exposure tosimazine. In summary, maternal exposure to simazine induced dysfunction of malereproductive system in mice offspring. Additional studies for the human risk assessmentof simazine are required. This work was supported by the Priority Research CentersProgram (2009-0093821) through the National Research Foundation of Korea (NRF) ofthe Ministry of Education, Science and Technology and by a grant (A084923) from theKorea Healthcare Technology R&D Project from the Ministry of Health, Welfare andFamily Affairs.U-18-51Involvement of yeast homolog MOH1 of human YPEL5 gene in DNAdamage-induced apoptosis in the budding yeast SaccharomycescerevisiaeU-18-53Apoptogenic activity of 2α,3α-dihydroxyurs-12-ene-28-oic acid fromPrunella vulgaris var. lilacina is mediated via mitochondria-dependentactivation of caspase cascade regulated by Bcl-2 in human acuteleukemia Jurkat T cellsHyun Ju Woo¹, Do Youn Jun², Ji Young Lee¹, Jung Yi Lee¹, Mi Hee Woo³, ChaeHa Yang⁴, Young Ho Kim¹ , *¹Laboratory of Immunobiology, School of Life Science and Biotechnology, College of NaturalSciences, Kyungpook National University, Daegu 702-701, Korea, ²Institute of Life Science andBiotechnology, Kyungpook National University, Daegu, Korea, ³Department of Pharmacology,College of Pharmacology, Daegu Catholic University, Kyeongsan, Korea, ⁴Department of OrientalMedicine, College of Oriental Medicine, Daegu Hanny University, Daegu, KoreaThis study was performed to investigate the apoptotic effect of 2α,3α-dihydroxyurs-12-en-28-oicacid (DHURS), purified from the spikes of Prunella vulgaris var. lilacina, on human acute leukemiaJurkat T cells and underlying apoptotic signaling mechanism. Treatment of Jurkat T cells withDHURS (20-25 mg/ml) caused cytotoxicity and apoptotic DNA fragmentation along with Δψmloss, mitochondrial cytochrome c release, activation of caspase-9, -7, -3, and -8, and PARPdegradation. However, these apoptotic events were abrogated by overexpression of Bcl-2.Pretreatment of the cells with the pan-caspase inhibitor, the caspase-9 inhibitor or the caspase-3inhibitor could block the activation of caspase-7 and -8, and PARP degradation, but not the Δψmloss, activation of caspase-9 and -3. Both FADD- and caspase-8-positive wild-type Jurkat cloneA3, FADD-deficient Jurkat clone I2.1, and caspase-8-deficient Jurkat clone I9.2 exhibited similarsusceptibilities to the cytotoxicity of DHURS. These results indicate that DHURS-inducedapoptogenic activity in Jurkat T cells, which was less potent in normal peripheral T cells, wasmediated by Δψm loss, mitochondrial cytochrome c release, and subsequent activation ofcaspase-9 and -3, caspase-7 and -8, which could be regulated by Bcl-2.Ji Young Lee¹, Do Youn Jun², Cho Rong Han¹, Young Ho Kim¹¹School of Life Science and Biotechnology, College of Natural Sciences, Kyungpook NationalUniversity, Daegu 702-701, Korea, ²Institute of Life Science and Biotechnology, KyungpookNational University, Daegu 702-701, KoreaThe homolog of Drosophila yippee protein is known to be highly conserved amongeukaryotes from yeast to human. For five members of the human YPEL family, YPEL5 isevolutionarily distinct from other four members, YPEL1 through YPEL4, especially.However, their functional roles are still poorly understood. To understand the role ofyippee protein, we have employed the budding yeast (Saccharomyces cerevisiae) mutantpossessing disrupted yeast homolog (MOH1; YBL049W) of yippee protein gene, andcompared its physiological characteristics with those of the wild-type strain. The mutantfor the MOH1 gene exhibited an enhanced resistance to UVC (254 nm) irradiation andgenotoxic agents as compared to the wild-type. This phenomenon was abrogated whenthe disrupted MOH1 gene in the mutant was restored by transformation of the functionalgene. The level of MOH1 mRNA in the wild-type was upregulated in response to UVCirradiation and genotoxic agents. And exposed phosphatidylserine was detected byreaction with annexin V-FITC and PI staining after UVC treated. Our findings provideevidence for functional conservation of YPEL5 protein between lower and highereukaryotes, which can confer apoptotic cell death to DNA damage in S. cerevisieae.348 Korean Society for Biochemistry and Molecular Biology