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가수분해형 탄닌 1-desgalloylrugosin-F 에 의한 100kDa 세포질 포스포리파아제 A2 활성억제효과
진미령(Mi Reyoung Chin),신혜숙(Hye Sook Shin),정광묵(Kwang Mook Jung),강미선(Mi Sun Kang),이민원(Min Won Lee),김대경(Dae Kyong Kim) 대한약학회 2000 약학회지 Vol.44 No.1
To examine whether DGRF inhibits cPLA2 activity in vitro, we purified a 100kDa cPLA2 enzyme from porcine spleen and performed an inhibition study at two concentrations of 5.0 and 50.0mcM 1-stearoyl-2-[1-14C]arachidonoyl-sn-glycero-3-phosphocholine as a substrate to rule out an apparent inhibition due to "substrate depletion". Here we reported that DGRF inhibited cPLA2 activity with ID50 of 3.2mcM and virtually complete inactivation of the enzyme occurred at 60mcM. Interaction experiment between enzyme protein and inhibitor by ultrafiltration method indicated that 1-desgalloylrugosin-F inactivates cPLA2 enzyme by an irreversible mechanism.
Inhibition of a Neutral Form of Sphingomyelinase by Alkylthioureido-1,3-propandiols, KY353X Series
( Sang Mi Jung ),( Eui Man Jeong ),( Dong Hwawn Jo ),( Mi Reyoung Chin ),( Hyung Jin Jun ),( Yong Hyun Kim ),( Hyung Jun Jeon ),( Dong Hun Lee ),( Mi Ja Park ),( Mi Jung Oh ),( Chul Bu Yim ),( Dae Kyo 한국응용약물학회 2003 Biomolecules & Therapeutics(구 응용약물학회지) Vol.11 No.3
Shin, Hae Sook,Chin, Mi-Reyoung,Kim, Jung Sun,Chung, Jin-Ho,Ryu, Chung-Kyu,Jung, Sung Yun,Kim, Dae Kyong 梨花女子大學校 藥學硏究所 2002 藥學硏究論文集 Vol.- No.11
It has become evident that a Ca^2+-dependent release ofarachidonic acid (AA) and subsequent fermation of bioac-tive lipid mediators such as prostag1andins and leukot.rienes in red blood cella (RBCa) can modify physiologicalfunctions of neighboring RBCs and platelets. Here we iden-tified a novel type of cytosolic PLA_2 in bovine and humanRBCe and purified it to apparent homogeneity with a14,000-fold purification. The purified enzyme, termedrPLA_2, hgs a molecular mass of 42 kDa and reveals bio-ehemical properties similar to group IV cPLA_2, but showadifferent profiles from cPLA_2 in several column chromatog-raphies. Moreover, rPLA_2 did not react with any of anti-cPLA_2 and anti-sPLA_2 antibodies and wae identified as anunknown protein in matrix-assisted laser desorption/ionization time-of-flight mass spectrometric analysis, Diva-lent metal ions tested exhibited similar effecte betweenrPLA_2 anf cPLA_2, whereas mercurials inhibited CPLA_2 buthad no effect on rPLA_2 Antibody against the 42-kDa pro-tein not only precipitated the rPLA_2 activity, but also re-acted with the 42-kDa protein from bovine and humanRBCs In Immunoblot analysis. The 42-kDa protein bandwas selectively detected in murine fetal livercells known asa type of progenitor cells of RBCs. It was found that EA4, aderivative of quinone newly developed as an inhibitor forrPLA_2, inhibited a Ca^2+ ionophore-induced AA release fromhumam and bovine RBCs, indicating that this enzyme isresponsible for the Ca^2+-dependent AA release from mam-malian RBCs. Finally, erythroid progenitor cell assay uti-lizing diaminobenzidine staining of hemoglobinized fetalliver celIs shewed that rPLA_2 detectable in erythroid cellswae down-regulated when differentiated to non-erythroidcells. Together, our results suggest that the 42-kDa rPLA_2identified as a novel form of Ca^2+-dependent PLA_2 may playan important role in hemostasis, thrombosis, and/or eryth-ropoiesis through the Ca^2+-drpendent release of AA.
치매 치료제 염산 디히드로에보다이아민의 생식 및 발생 독성
성이숙(Yi Sook Sung),정성윤(Sung Yun Jung),서영득(Young Deog Seo),진미령(Mi Reyoung Chin),최봉웅(Bong Woong Choi),장병모(Byeung Mo Chang),김대경(Dae Kyong Kim) 대한약학회 2002 약학회지 Vol.46 No.6
Dehydroevodiamine-HCI (DHED), which is a component separated from Evodia rutaecarpa Bentham, has novel anticholinesterase and antiamnesic activities in a scopolamine- induced amnesia model. Several studies suggest that DHED might be an effective drug for Alzheimer's disease and a vascular type of dementia. DHED was at dose levels of 0, 50, 100 and 200 mg/kg/day administered intraperitoneally to Sprague-Dawley male rats for 60 days before mating and to females from 14 days before mating to 7 days after mating. Effects of the DHED on general symptom and reproductive performance of parent animals and embryonic development were examined. In male parents, whereas no death was observed, reduction in the increase rate of body weight was found at 200 mg/kg. In female parents, both of the mating performance and the fertility of parent animals were decreased at 200 mg/kg, but not significantly. In 200 mg/kg treated group, the fetal death rate was increased but total fetuses showed no changes compared to the control group. There were no malformed F1 fetuses in all groups.
치료제 Dehydroevodiamine • HCl(DHED) 의 변이원성 연구
성이숙(Yi Sook Sung),정성윤(Sung Yun Jung),정주연(Ju Yeon Jeong),채규영(Gyu Young Chae),진미령(Mi-Reyoung Chin),최봉웅(Bong Woong Choi),장병모(Byeung Mo Chang),김대경(Dae Kyong Kim) 대한약학회 2002 약학회지 Vol.46 No.3
Dehydroevodiamine HC1 (DHED), which is a component separated from Evodia rutaecarpa Bentham, has novel anticholinesterase and antiamnesic activities in th e scopolamine-induced amnesia model. Several studies suggest that DHED might be an effective drug for the Alzheimer's disease and the vascular type of dementia. In order to evaluate the mutagenic potential of DHED, Salmonella typhimurium reversion assay, chromosomal aberration test on Chinese hamster lung cells, in vivo micronucleus assay using mouse bone marrow cells, and comet assay were performed. DHED did not increase the number of revertant in the reverse mutation test using Salmonella typhimurium TA1535, TA1537, TA98, TA100. DHED HC1, at concentration of 5 and 10 jag/m/, increased the number of chromosome aberrated Chinese hamster lung cells with 5 and 10%, respectively. In mouse micronucleus test, no significant increase in the occurrence of micronucleated polychromatic erythrocyte was observed in ICR mice orally administered with DHED. DHED was tested for ability to induce genotoxic effect in L5178Y cells (mouse lymphoma cells) using the single cell gel electrophoresis assay (comet assay). In comet assay, tail moment did not increase in L5178Y cells treated with 10,100, 300 uM DHED .