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Radicicol이 신경세포에서 베타 아밀로이드 전구단백질의 대사에 미치는 영향
임재윤,이일화,이경아,공두균,최부진,이충수,은재순,Leem, Jae-Yoon,Lee, Ri-Hua,Lee, Kyung-A,Gong, Du-Gyun,Choi, Bu-Jin,Lee, Choong-Soo,Eun, Jae-Soon 대한약학회 2007 약학회지 Vol.51 No.4
Alzheimer’s disease (AD) is characterized pathologically by the presence of intracellular neurofibrillary tangles and deposition of ${\beta}-amyloid $ (A ${\beta}$) peptides, which are generated by processing of amyloid precursor protein (APP). It is urgent to develop effective therapies for the treatment of AD, since our society rapidly accelerate aging. A${\beta}$ peptides have been believed to be neurotoxic and now are also considered to have effects on the mechanism of memory formation. In this study, effects of radicicol on the metabolism of APP were analyzed. Radicicol inhibited the secretion of A${\beta}$ from the Neuro2a cell line (APPswe cell) expressing APPswe. Beta-site APP cleaving enzyme (BACE) fluorescence resonance energy transfer (FRET) assay revealed that it inhibited BACE activity in a dose dependently manner. Immunoblotting study showed that it inhibited intracellular heat shock protein (HSP)90 and it increased the secretion of HSP90 from the APPswe cells. We suggest that radicicol inhibits APP metabolism and Ap generation by the means of HSP90 inhibitory mechanism and partially BACE inhibitory mechanism. This is the first report that radicicol inhibits the secretion of A${\beta}$ peptides from neuroblastoma cells.
신규 항균물질 5-S-GAD(N-beta-alanyl-5-S-glutathionyl-3,4-dihydroxyphenylalanine)의 합성 및 생리활성
임재윤(Jae Yoon Leem),박호용(Ho Yong Park),Natori Shunji 대한약학회 1998 약학회지 Vol.42 No.3
We had already reported that we purified N-beta-alanyl-5-S-glutathionyl-3,4-dihydroxyphenylalanine (5-S-GAD), a novel antibacterial substance from the immunized adult Sarcophaga peregrina (Flesh fly). We found that the antibacterial activity of synthetic 5-S-GAD is equal to that of authentic 5-S-GAD without a specificity of antibacterial activity against Gram positive and Gram negative. Significant synergism was detected between 5-S-GAD and streptomycin against streptomycin resistant strain E.coli K12 594. It has an antitumor activity against several tumor cell lines at a concentration of 100mcM. However, no cytotoxic activity against murine macrophage was detected at a concentration of 500mcM. Furthermore, haemolytic activity against sheep erythrocytes was not detected at the same concentration. We suggest that the S-conjugation of glutathion with dihydroxyphenylalanine might be important to increase antibacterial activity of dihydroxyphenylalanme.
3-페닐-1-이소퀴놀린아민이 신경세포에서 베타 아밀로이드 전구단백질의 대사에 미치는 영향
임재윤(Jae-Yoon Leem),조원제(Won-Jea Cho) 대한약학회 2010 약학회지 Vol.54 No.6
Alzheimer's disease (AD) is characterized pathologically by the presence of intracellular neurofibrillary tangles and deposition of β-amyloid (Aβ) peptides, which are generated by processing of amyloid precursor protein (APP). It is urgent to develop effective therapies for the treatment of AD, since our society rapidly accelerate aging. Aβ peptides have been believed to be neurotoxic and now are also considered to have effects on the mechanism of memory formation. Recently, we investigated that a quinoline compound from natural product reduced the secretion of Aβ from the neuroblastoma N2a cells (NL/N cell line) overexpressing APPswe. In this study, 3-phenyl-1-isoquinolinamine, a synthetic isoquinoline compound was analyzed to determine its effects on the metabolism of APP. It inhibited the secretion of Aβ peptides from the N2a NL/N cell line. Beta-site APP cleaving enzyme (BACE) fluorescence resonance energy transfer (FRET) assay revealed that it inhibited BACE activity in a dose dependent manner. Immunoblotting study showed that it inhibited APP stabilization and expression and it slightly increased the stablization and the expression of γ-secreatase component from the N2a NL/N cell line. We suggest that 3-phenyl-1-isoquinolinamine inhibits APP metabolism and Aβ generation by the means of BACE inhibitory mechanism. This is the first report that 3-phenyl-1-isoquinolinamine inhibits the secretion of Aβ peptides from neuroblastoma cells.
GC-MS 기반 대사체학 기법을 이용한 택사의 산지판별모델
임재윤(Jae-Yoon Leem) 대한약학회 2016 약학회지 Vol.60 No.1
Traditional Korean medicines may be managed more scientifically, through the development of logical criterion to verify their cultivation region. It contributes to advance the industry of traditional herbal medicines. Volatile compounds were obtained from 14 samples of domestic Taeksa and 30 samples of Chinese Taeksa by steam distillation. The metabolites were identified by NIST mass spectral library in the obtained gas chromatography/mass spectrometer (GC/MS) data of 35 training samples. The multivariate statistical analysis, such as Principal Component Analysis (PCA), Partial Least Squares Discriminant Analysis (PLS-DA), and Orthogonal Partial Least Squares Discriminant Analysis (OPLS-DA), were performed based on the qualitative and quantitative data. Finally trans-(2,3-diphenylcyclopropyl)methyl phenyl sulfoxide (47.265 min), 1,2,3,4-tetrahydro-1-phenyl-naphthalene (47.781 min), spiro[4-oxatricyclo[5.3.0.0.(2,6)]decan-3-one-5,2'-cyclohexane] (54.62 min), 6-[7-nitrobenzofurazan-4-yl]amino-morphinan-4,5-epoxy (54.86 min), p-hydroxynorephedrine (55.14 min) were determined as marker metabolites to verify candidates for the origin of Taeksa. The statistical model was well established to determine the origin of Taeksa. The cultivation areas of test samples, each 3 domestic and 6 Chinese Taeksa were predicted by the established OPLS-DA model and it was confirmed that all 9 samples were precisely classified.
삼릉전이 생쥐에 이식된 L1210 세포의 증식에 미치는 영향
전용근,임재윤,송정모,은재순,Jeon Yong Keun,Leem Jae Yoon,Song Jung Mo,Eun Jae Soon 대한동의생리학회 2005 동의생리병리학회지 Vol.19 No.3
We studied effects of Samreungjeon water extract (SE) on the proliferation of transplanted-L1210 cells to mice. Samreungjeon is composed of Scirpi Tuber, Zedoariae Rhizoma, Aurantii immaturi Pericarpium, Pinelliae Tuber and Hordei Fructus Germinatus. When SE (500 mg/kg) was administered orally once a day for 7 days after transplantation of L1210 cells to mice, the proliferation of transplanted-L1210 cells was decreased and DNA fragmentation of transplanted-L1210 cells was induced. Also, DNA fragmentation of L1210 cells was enhanced by co-culture with the peritoneal macrophages obtained from SE-administered mice and was partly inhibited by L-NMMA in vitro. SE enhanced the production of nitric oxide from murine peritoneal macrophages in vitro and in vivo. These results suggest that SE partly induces apoptosis of transplanted-L1210 cells via production of nitric oxide from macrophages.