11:10-12:00, Rm 103

Chemical biology and drug discoveryD-17-25Comparision of skin penetration between ascorbic acid and itsderivatives in hairless mice skinMin Young Kang, Insook Han, Jung-Chul KimDepartment of Immunology, School of Medicine, Kyungpook National University, Daegu 700-422,KoreaL-ascorbic acid(AA) has been known to have skin whitening effect by anti-oxidation.Recently it has also been reported to improve hair growth and increase the density ofdermal papilla of hair follicle. However, AA is unstable and has some limitation in skinusage and delivery. Thus, the stable derivatives of AA are applied to overcome theproblems. In this study, skin penetration of AA-2-phosphate magnesium salt (AP-Mg)containing hydrophilic moiety of phosphate and AA-6-palmitate (A-Pal) includinghydrophobic moiety of palmitate, were compared with AA using Franz cell with hairlessmice skin. The substances penetrated through the skin or sustained in skin wereanalyzed by HPLC. The results showed that the order of skin penetration increases : AP-Mg < A-Pal < AA while that of skin retention increases : AP-Mg < AA < A-PalD-17-287,8-dihydro-8-oxo-2’-deoxyguanosine is a strong scavenger of hydroxylradicals, peroxynitrite and singlet oxygenSeong-Hee Ko¹, Jin-Ku Lee², Ki-Baik Hahm³, Sang-Kyu Ye²and Myung-HeeChung²¹Major in Food and Nutrition, College of Human Ecology, Sookmyung Women’s University,²Department of Pharmacology, Seoul National University College of Medicine, ³Laboratory of CellRegulation and Carcinogenesis, Lee Gil Ya Cancer and Diabetes Research Institute, GachonUniversity of Medicine and ScienceAn attempt was made to test the anti-oxidant activity of 7,8-dihydro-8-oxo-2’-deoxyguanosine (8-oxo-dG). 8-Oxo-dG abolished 5,5-dimethylpyrroline-N-oxide-OHsignal completely in electron spin resonance spectroscopy and inhibited HO∙-inducedoxidation of 2,7-dichlorodihydrofluorescein (DCHF). 8-oxo-dG also inhibited DCHFoxidations by peroxynitrite and low density lipoprotein oxidation by 1 O2. In all oxidationsystems used, 8-oxo-dG showed even stronger inhibition than the anti-oxidants tested,including synthetic:Trolox, N-acetylcysteine, present in the diets: ascorbate, β-carotene,(+)-catechin hydrate, quercetin dihydrate, and synthesized in the body: α-lipoic acid, β-estradiol, α-ketoglutaric acid, guanosine, L-carnosine, billirubin, melatonin and uric acid.8-Oxo-dG also showed effective prevention against the UV-induced skin reactions inmice, including increase of protein carbonyl contents, activations of ERK and p38,increase of MMP-9 and -13 expressions, and epidermal hyperplasia. Here, 8-oxo-dG wasalso more effective than the anti-oxidants tested. The potent anti-oxidant activity of 8-oxodGmight be a beneficial property that might be used for the modulation of cell functionsor treatment of various ROS associated disorders.D-17-26Effect of galangin on the formation of various prostaglandins producedby COXs in vitro and in vivoHyoung-Woo Bai, Jin Hong Kim, Seung Sik Lee and Byung Yeoup ChungAdvanced Radiation Technology Institute (ARTI), Korea Atomic Energy Institute (KAERI),Jeongeup-Si 580-185, KoreaRecently we showed that some of the dietary bioflavonoids could function as naturallyoccurring,high-affinity reducing co-substrates for COXs. Further computational molecularmodeling study revealed that these compounds could tightly bind to the peroxidase activesites of the enzymes, with their B-ring hydroxyl groups donating two electrons to theheme component. Based on these finings, it is predicted that some dietary compoundsthat lack the B-ring hydroxyl groups may function as antagonists that will block thestimulatory effect of the active bioflavonoids, and this idea was tested in the presentstudy. We found that galangin, a representative bioflavonoid without any hydroxyl groupin its B-ring, could strongly inhibit, both in vitro and in vivo, quercetin’s stimulation of thecatalytic activity of COX I and II. Computational modeling study showed that galangincould tightly bind to the peroxidase sites of COX I and II, but it could not serve as areducing co-substrate as did quercetin. As such, galangin could selectively block thebinding of the stimulator, and thereby reduced its stimulatory activity. Our findingsuggests that galangin and other bioflavonoids with similar structural features may serveas inhibitors of the COX’s catalytic activity.D-17-27Inhibition of double-stranded RNA-induced inducible nitric oxidesynthase expression by fraxinellone and sauchinone in murine microgliaEun Hee Yi, Chang Seok Lee, Yun Sook Min, Min Jeoung Lee, Ji Won Choi andSang-Kyu YeDepartment of Pharmacology, Seoul National University College of Medicine, andIschemic/Hypoxic Disease Institute, Seoul National University College of Medicine, 28 Yongon-Dong, Chongno-Gu, Seoul 110-799, KoreaFraxinellone and sauchinone, isolated from natural substance, are known to have an antiinflammatoryeffect in inflammatory conditions. However, the anti-inflammatory actions ofthese compounds have been insufficiently demonstrated in viral-inducedneuroinflammation. A viral component (dsRNA) triggers a TLR3-dependent inflammatoryresponse that stimulates pro-inflammatory mediators in the brain. In present study, weinitially examined the biological effects of fraxinellone and sauchinone on antiinflammatoryactions in dsRNA-stimulated microglia. Both compounds inhibited dsRNAinducediNOS expression, a major pro-inflammatory enzyme. To demonstrate themechanism of inhibitory effect on iNOS expression, we further examined the signalingpathway induced by dsRNA in microglia. Our data show that dsRNA promotes theexpression of STAT1/3 identified as major inflammatory transcription factors as well asactivates JNK in an early time. Moreover, both compounds suppressed activation of JNK-STAT1/3 signaling pathway. These results suggest that an anti-inflammatory effect byfraxinellone and sauchinone is mediated via blockade of the JNKSTAT1/3-iNOS signalingpathway in viral-infected microglia.D-17-29Protective effect of selenium against ethanol-induced gastric mucosaldamages in ratsJeong-Hwan Kim 1 , Shin-Hyung Park 2 , Byung-Woo Kim 1, 3, 5 1, 4, 5, Soo-Wan Nam and1, 5, 6Yung-Hyun Choi¹Department of Biomaterial Control, ³Department of Life Science and Biotechnology, ⁴Departmentof Biotechnology and Bioengineering and 5 Blue-Bio Industry RIC, Dong-Eui University, Busan614-714, ²Department of Pathology, 6 Department of Biochemistry and Research Institute ofOriental Medicine, Dong-Eui University College of Oriental Medicine, Busan 614-052, KoreaIt was investigated the protective effect of selenium against ethanol-induced gastricmucosal damages in rats. The gastric mucosal damages were induced by oraladministration with ethanol for 3 days, and 80% ethanol treatment was determined to bethe optimal condition for induction of gastric damage. To identify the protective effect ofselenium on ethanol-induced gastric mucosal damage, selenium was pretreated, andthen gastric damage was induced by ethanol treatment. Selenium showed the protectiveeffect against ethanol-induced gastric mucosal damages in a dose dependent manner.Especially, 100 µg/kg selenium showed the highest effect of gastroprotection. In addition,selenium markedly attenuated ethanol-induced lipid peroxidation in gastric mucosa andincreased activities of radical scavenging enzymes, such as superoxide dismutase,catalase, and glutathione peroxidase. A histological data showed that 100 µg/kg seleniumdistinctly reduced the depth and severity of the ethanol-induced gastric damage. Theseresults clearly demonstrate that selenium inhibits ethanol-induced gastric mucosaldamages through prevention of lipid peroxidation and activation of enzymatic radicalscavenging. [Supported by Blue-Bio Industry RIC at Dong-Eui University as a RIC (08-06-07) program of KIAT]D-17-30Anti-inflammatory effects of glycoprotein isolated from Laminariajaponica in lipopolysaccharide-stimulated BV2 microglial cellsHye Young Park 1 , Min Ho Han 2 , Nam Deuk Kim 1 , Taek-Jeong Nam 3 and Yung HyunChoi 2, 4¹Department of Pharmacy, Pusan National University, Busan 609-735, ²Department ofBiomaterial Control and Blue-Bio Industry RIC, Dongeui University Graduate School, Busan 614-714, ³Department of Food Science and Biotechnology, Pukyong National University, Busan 608-737, ⁴Department of Biochemistry and Research Institute of Oriental Medicine, DongeuiUniversity College of Oriental Medicine, Busan 614-052, KoreaChronic microglial activation endangers neuronal survival through release of various toxicpro-inflammatory molecules; therefore, negative regulators of microglial activation havebeen identified as potential therapeutic candidates for use in treatment of manyneurological diseases. In this study, we conducted an investigation of the inhibitoryeffects of glycoprotein isolated from Laminaria japonica (LJGP) on production of LPSinducedpro-inflammatory mediators in BV2 microglial cells. Data from the study indicatedthat treatment with LJGP resulted in significant inhibition of excessive production of nitricoxide (NO) and prostaglandin E2 (PGE2) in LPS-stimulated BV2 cells. LJGP alsoattenuated expression of inducible nitric oxide synthase (iNOS), cyclooxygenase (COX)-2, and pro-inflammatory cytokines, including interleukin-1β(IL-1β) and tumor necrosisfactor (TNF)-α. In addition, LJGP exhibited anti-inflammatory properties by suppression ofnuclear factor-kappaB (NF-κB) activation and downregulation of ERK, p38 MAPK, andAKT pathways. These findings suggest LJGP may provide neuroprotection throughsuppression of the proinflammatory pathway in activated microglia. [Supported by theproject funded by the Ministry of Land, Transport and Maritime Affairs]222 Korean Society for Biochemistry and Molecular Biology