http://chineseinput.net/에서 pinyin(병음)방식으로 중국어를 변환할 수 있습니다.
변환된 중국어를 복사하여 사용하시면 됩니다.
Mechanism for the Differentiation of EoL-1 Cells into Eosinophils by Histone Deacetylase Inhibitors
Kaneko, Motoko,Ishihara, Kenji,Takahashi, Aki,Hong, JangJa,Hirasawa, Noriyasu,Zee, OkPyo,Ohuchi, Kazuo S.Karger 2007 International archives of allergy and immunology Vol.143//SUP1 No.-
<P><I>Background:</I> EoL-1 cells have a <I>FIP1L1-PDGFRA</I> fusion gene which causes the transformation of eosinophilic precursor cells into leukemia cells. Recently, we suggested that the induction of differentiation of EoL-1 cells into eosinophils by the HDAC inhibitors apicidin and n-butyrate is due to the continuous inhibition of HDACs. However, neither apicidin nor n-butyrate inhibited the expression of FIP1L1-PDGFRA mRNA, although both these inhibitors suppressed cell proliferation. Therefore, in this study, we analyzed whether the levels of FIP1L1-PDGFRα protein and phosphorylated-Stat5 involved in the signaling for the proliferation of EoL-1 cells are attenuated by HDAC inhibitors. <I>Methods:</I> EoL-1 cells were incubated in the presence of apicidin, TSA or n-butyrate. FIP1L1-PDGFRα and phosphorylated-Stat5 were detected by Western blotting. <I>Results:</I> Treatment of EoL-1 cells with apicidin at 100 n<I>M</I> or n-butyrate at 500 μ<I>M</I> decreased the levels of FIP1L1-PDGFRα protein and phosphorylated-Stat5, while that with trichostatin A at 30 n<I>M</I> did not. <I>Conclusions:</I> The decrease in the level of FIP1L1-PDGFRα protein caused by apicidin and n-butyrate might be one of the mechanisms by which EoL-1 cells are induced to differentiate into eosinophils by these HDAC inhibitors.</P><P>Copyright © 2007 S. Karger AG, Basel</P>
Lee, Yeon Sil,Lee, Sanghyun,Lee, Hye Seung,Kim, Bak-Kwang,Ohuchi, Kazuo,Shin, Kuk Hyun Pharmaceutical Society of Japan 2005 Biological & pharmaceutical bulletin Vol.28 No.5
<P>The inhibitory effects of compounds from <I>Salicornia herbacea</I> (Chenopodiaceae) on rat lens aldose reductase (RLAR) and sorbitol accumulation in streptozotocin-induced diabetic rat tissues were investigated. The various fractions from the MeOH extract of <I>S. herbacea</I> were tested for their effects on RLAR <I>in vitro</I>. Among them, the EtOAc fraction was found to exhibit a potent RLAR inhibition (IC<SUB>50</SUB>=0.75 μg/ml), from which an active principle as a potent AR inhibitor was isolated and its chemical structure was elucidated as isorhamnetin-3-<I>O</I>-β-<SMALL>D</SMALL>-glucoside (1) by spectral analysis. Compound 1 exhibited a potent RLAR inhibition <I>in vitro</I>, its IC<SUB>50</SUB> being 1.4 μ<SMALL>M</SMALL>. Compound 1, when administered orally at 25 mg/kg in streptozotocin (STZ)-induced diabetic rats, caused not only a significant inhibition of serum glucose concentration but also sorbitol accumulation in the lenses, red blood cells (RBC), and sciatic nerves. These results indicate that compound 1 from <I>S. herbacea</I> is a leading compound for further study as a new drug for the prevention and/or treatment of diabetes and its complications.</P>
Anti-angiogenic and Anti-tumor Activities of 2′-Hydroxy-4′-methoxychalcone
Lee, Yeon Sil,Lim, Soon Sung,Shin, Kuk Hyun,Kim, Yeong Shik,Ohuchi, Kazuo,Jung, Sang Hoon Pharmaceutical Society of Japan 2006 Biological & pharmaceutical bulletin Vol.29 No.5
<P>In the present study, we evaluated the <I>in vitro</I> and <I>in vivo</I> anti-angiogenic and anti-tumor activities of 2′-hydroxy-4′-methoxychalcone (HMC). HMC decreased angiogenesis in both chick embryos in the chorioallantoic membrane assay and basic fibroblast growth factor (bFGF)-induced vessel formation in the mouse Matrigel plug assay. This compound also reduced the proliferation of calf pulmonary arterial endothelial cells and was found to possess relatively weak gelatinase/collagenase inhibitory activity <I>in vitro</I>. HMC, when administered subcutaneously at the dose of 30 mg/kg for 20 d to mice implanted with murine Lewis lung carcinoma, caused a significant inhibition of tumor volume by 27.2%. Intraperitoneal (i.p.) treatment at the same dosage for 10 d to ICR mice bearing sarcoma 180 caused a significant suppression in tumor weight by 33.7%. Taken together, out data demonstrate that the anti-angiogenic activities of HMC might be due to anti-proliferative activity under inhibition of the induction of COX-2 enzyme. Furthermore, the results suggest that the potent anti-angiogenic activity of HMC seems to be the possible mechanism of action in these animal models of solid tumors.</P>
Protein Glycation Inhibitors from the Fruiting Body of <i>Phellinus linteus</i>
Lee, Yeon Sil,Kang, Young-Hee,Jung, Ju-Young,Lee, Sanghyun,Ohuchi, Kazuo,Shin, Kuk Hyun,Kang, Il-Jun,Park, Jung Han Yoon,Shin, Hyun-Kyung,Lim, Soon Sung Pharmaceutical Society of Japan 2008 BIOLOGICAL & PHARMACEUTICAL BULLETIN Vol.31 No.10
<P>To characterize active principles for prevention and treatment of diabetic complications, the isolation of protein glycation inhibitors from the fruiting body of <I>Phellinus linteus</I> was conducted <I>in vitro</I> using the model systems of hemoglobin-δ-gluconolactone (early stage), bovine serum albumin-methylglyoxal (middle stage), and <I>N</I><SUP>α</SUP>-acetyl-glycyl-lysine methyl ester-<SMALL>D</SMALL>-ribose (last stage) assays. Nine compounds were isolated from the active ethylacetate fraction of the fruiting body and identified as protocatechuic acid (1), protocatechualdehyde (2), caffeic acid (3), ellagic acid (4), hispidin (5), davallialactone (6), hypholomine B (7), interfungins A (8), and inoscavin A (9) by spectroscopic analyses. At the early stage of protein glycation, compounds 6, 8, and 9 exhibited inhibitory activity on hemoglobin A<SUB>1C</SUB> formation. For the middle stage, compounds 2, 6, and 9 showed a significant inhibitory effect on methylglyoxal-medicated protein modification and their IC<SUB>50</SUB> values were 144.28, 213.15, and 158.66 μ<SMALL>M</SMALL>, respectively. At the last stage of glycation, compound 8 was found to be a potent inhibitor of the cross-linking of proteins, which was more effective than that of aminoguanidine, a well-known inhibitor for advanced glycation end products. Consequently, compound 8 showed the most potent inhibitory effects at each stage of protein glycation. This mechanism may help to provide a protective effect against hyperglycemia-mediated protein damage.</P>
Jung, Sang Hoon,Park, Soo Young,Kim-Pak, Youngmi,Lee, Hong Kyu,Park, Kyong Soo,Shin, Kuk Hyun,Ohuchi, Kazuo,Shin, Hyun-Kyung,Keum, Sam Rok,Lim, Soon Sung The Pharmaceutical Society of Japan 2006 Chemical & pharmaceutical bulletin Vol.54 No.3
<P>Fifteen chalcones and three thiazolidinedione (TZD) chalcones were prepared to evaluate their peroxisome proliferator-activated receptor-γ (PPAR-γ) ligand-binding activities. Among the three TZDs, one compound possessed PPAR-γ transactivation potential, while the others showed antagonistic activity against PPAR-γ transactivation. Among the chalcones, compound 5 was the most potent, and structure–activity relationship studies indicated that a methoxyl group in position C-4 and hydroxyl group in position C-4′ or 5′ in chalcone plays a key role in determining the potency of PPAR-γ activation.</P>
Hong, JangJa,Yokomakura, Aya,Nakano, Yasuhiro,Ban, Hyun Seung,Ishihara, Kenji,Ahn, Jong-Woong,Zee, OkPyo,Ohuchi, Kazuo Williams Wilkins 2005 The Journal of Pharmacology and Experimental Thera Vol.312 No.3
<P>We previously reported that apicularen A [2,4-heptadienamide, N-[(1E)-3-[(3S,5R,7R,9S)-3,4,5,6,7,8,9,10-octahydro-7,14 dihydroxy-1-oxo-5,9-epoxy-1H-2-benzoxacyclododecin-3-yl]-1 propenyl]-, (2Z,4Z)-(9CI)], a highly cytostatic macrolide isolated from the myxobacterial genus Chondromyces, induces apoptosis in the mouse leukemic monocyte cell line RAW 264.7. To analyze the action mechanism of apicularen A for the induction of apoptosis, effects of apicularen A on nitric oxide (NO) production in RAW 264.7 cells were examined. It was demonstrated that apicularen A at 10 and 100 nM induced nitrite production, whereas apicularen B [2,4-heptadienamide, N-[(1E)-3-[(3S,5R,7R,9S)-7-[[2-(acetylamino)-2-deoxy-beta-d-glucopyranosyl]oxy]-3,4,5,6,7,8,9,10-octahydro-14-hydroxy-1-oxo-5,9-epoxy-1H-2-benzoxacyclododecin-3-yl]-1 propenyl]-, (2Z,4Z)-(9CI)], an N-acetyl-glucosamine glycoside of apicularen A, had no effect at 100 nM. The apicularen A-induced nitrite production was accompanied by an increase in the level of inducible nitric-oxide synthase (iNOS) and its mRNA and was suppressed by the NOS inhibitor N(G)-monomethyl-l-arginine acetate (l-NMMA). In addition, apicularen A activated nuclear factor-kappaB (NF-kappaB) and activator protein-1 (AP-1) and decreased the level of IkappaB-alpha and increased that of phosphorylated c-Jun N-terminal kinase (JNK). Furthermore, the apicularen A-induced nitrite production was suppressed by the NF-kappaB inhibitor Bay 11-7082 [(E)-3-(4-methylphenylsulfonyl)-2-propenenitrile] and the JNK inhibitor SP600125 [anthra[1,9-cd]pyrazol-6(2H)-one]. These findings suggested that apicularen A activates NF-kappaB and AP-1, thus triggering the expression of iNOS mRNA and iNOS protein and induces NO production. Finally, apicularen A decreased cell growth and survival and cell viability and disrupted the mitochondrial membrane potential. The addition of l-NMMA partially recovered the apicularen A-induced decrease in cell growth and survival and cell viability and the disruption of mitochondrial membrane potential. These findings suggested that NO produced by apicularen A treatment participate partially in the apicularen A-induced apoptosis in RAW 264.7 cells.</P>