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51.
Jae Yeon Kim Hyo Jin Lim Da Yeon Lee Ji Sun Kim Do Hee Kim Hwa Jin Lee Hee Doo Kim Raok Jeon Jae-Ha Ryu 《Bioorganic & medicinal chemistry letters》2009,19(3):937-940
The overproduction of nitric oxide (NO) and prostaglandin E2 (PGE2) causes neurodegenerative diseases, such as Alzheimer’s disease and Parkinson’s disease. Four lignans, (+)-eudesmin (1), (+)-magnolin (2), (+)-yangambin (3) and a new structure named as epimagnolin B (4) were isolated from Magnolia fargesii (Magnoliaceae) as the inhibitors of NO production in LPS-activated microglia. The most potent compound 4 inhibited the production of NO and PGE2 and the expression of respective enzyme iNOS and COX-2 through the suppression of I-κB-α degradation and nuclear translocation of p65 subunit of NF-κB. 相似文献
52.
Chung-Kyu Ryu Jung Yoon Lee Seong Hee Jeong Ji-Hee Nho 《Bioorganic & medicinal chemistry letters》2009,19(1):146-148
1H-Pyrrolo[3,2-g]quinoline-4,9-diones and 4,9-dioxo-4,9-dihydro-1H-benzo[f]indoles were synthesized and tested for in vitro antifungal activity against fungi. Among them tested, many compounds showed good antifungal activity. The results suggest that 1H-pyrrolo[3,2-g]quinoline-4,9-diones and 4,9-dioxo-4,9-dihydro-1H-benzo[f]indoles would be potent antifungal agents. 相似文献
53.
Hwangseo Park Young Jae Bahn Seong Eon Ryu 《Bioorganic & medicinal chemistry letters》2009,19(15):4330-4334
Cdc25 phosphatases have been considered as attractive drug targets for anticancer therapy due to the correlation of their overexpression with a wide variety of cancers. We have been able to identify 32 novel Cdc25 phosphatase inhibitors with micromolar activity by means of a structure-based de novo design method with the two known inhibitor scaffolds. Because the newly discovered inhibitors are structurally diverse and have desirable physicochemical properties as a drug candidate, they deserve further investigation as anticancer drugs. The differences in binding modes of the identified inhibitors in the active sites of Cdc25A and B are addressed in detail. 相似文献
54.
Guo Hua Jin Da Yeon Lee Ye-Jin Cheon Hyo Jin Gim Do Hee Kim Hee-Doo Kim Jae-Ha Ryu Raok Jeon 《Bioorganic & medicinal chemistry letters》2009,19(11):3088-3092
A series of phenylisothioureas were synthesized as inhibitors of NO production in lipopolysaccharide-activated macrophages. We investigated the effect of lipophilic moiety and N- or S-substituents of the phenylisothioureas on the activity. Inhibitory activities of carbazole-linked phenylisothioureas were superior to the corresponding simple phenylisothiourea derivatives. Among these compounds, 12b having N-ethyl and S-isopropyl groups on phenylisothiourea moiety was the most potent in the inhibition of NO production. They inhibited NO production through the suppression of the LPS-induced translocation of p65 subunit of NF-κB and the followed suppression of the iNOS protein and mRNA expression. 相似文献
55.
56.
Sun Jae Kwon Hak Chul Jin Soohyun Lee Myung Hee Nam Joo Hee Chung Soon Il Kwon Choong-Min Ryu Ohkmae K. Park 《The Plant journal : for cell and molecular biology》2009,58(2):235-245
Systemic resistance is induced by necrotizing pathogenic microbes and non-pathogenic rhizobacteria and confers protection against a broad range of pathogens. Here we show that Arabidopsis GDSL LIPASE-LIKE 1 (GLIP1) plays an important role in plant immunity, eliciting both local and systemic resistance in plants. GLIP1 functions independently of salicylic acid but requires ethylene signaling. Enhancement of GLIP1 expression in plants increases resistance to pathogens including Alternaria brassicicola , Erwinia carotovora and Pseudomonas syringae , and limits their growth at the infection site. Furthermore, local treatment with GLIP1 proteins is sufficient for the activation of systemic resistance, inducing both resistance gene expression and pathogen resistance in systemic leaves. The PDF1.2 -inducing activity accumulates in petiole exudates in a GLIP1-dependent manner and is fractionated in the size range of less than 10 kDa as determined by size exclusion chromatography. Our results demonstrate that GLIP1-elicited systemic resistance is dependent on ethylene signaling and provide evidence that GLIP1 may mediate the production of a systemic signaling molecule(s). 相似文献
57.
Makoto Fujii Kye Sook Yi Myung Jong Kim Sang Hoon Ha Sung Ho Ryu Pann‐Ghill Suh Hitoshi Yagisawa 《Journal of cellular biochemistry》2009,108(3):638-650
Phosphorylation of phospholipase C‐δ1 (PLC‐δ1) in vitro and in vivo was investigated. Of the serine/threonine kinases tested, protein kinase C (PKC) phosphorylated the serine residue(s) of bacterially expressed PLC‐δ1 most potently. It was also demonstrated that PLC‐δ1 directly bound PKC‐α via its pleckstrin homology (PH) domain. Using deletion mutants of PLC‐δ1 and synthetic peptides, Ser35 in the PH domain was defined as the PKC mediated in vitro phosphorylation site of PLC‐δ1. In vitro phosphorylation of PLC‐δ1 by PKC stimulated [3H]PtdIns(4,5)P2 hydrolyzing activity and [3H]Ins(1,4,5)P3‐binding of the PLC‐δ1. On the other hand, endogenous PLC‐δ1 was constitutively phosphorylated and phosphoamino acid analysis revealed that major phosphorylation sites were threonine residues in quiescent cells. The phosphorylation level and the species of phosphoamino acid were not changed by various stimuli such as PMA, EGF, NGF, and forskolin. Using matrix‐assisted laser desorption/ionization time‐of‐flight (MALDI‐TOF) mass spectrometry, we determined that Thr209 of PLC‐δ1 is one of the constitutively phosphorylated sites in quiescent cells. The PLC activity was potentiated when constitutively phosphorylated PLC‐δ1 was dephosphorylated by endogenous phosphatase(s) in vitro. Additionally, coexpression with PKC‐α reduced serine phosphorylation of PLC‐δ1 detected by an anti‐phosphoserine antibody and PLC‐δ1‐dependent basal production of inositol phosphates in NIH‐3T3 cells, suggesting PKC‐α activates phosphatase or inactivates another kinase involved in PLC‐δ1 serine phosphorylation to modulate the PLC‐δ1 activity in vivo. Taken together, these results suggest that PLC‐δ1 has multiple phosphorylation sites and phosphorylation status of PLC‐δ1 regulates its activity positively or negatively depends on the phosphorylation sites. J. Cell. Biochem. 108: 638–650, 2009. © 2009 Wiley‐Liss, Inc. 相似文献
58.
Pablo M. Peixoto Shin-Young Ryu Dawn Pietkiewicz Pruzansky Andrew Gilmore 《Biochemical and biophysical research communications》2009,390(1):38-725
The death of one cell can precipitate the death of nearby cells in a process referred to as the bystander effect. We investigated whether mitochondrial apoptosis generated a bystander effect and, if so, by which pathway. Microinjection with cytochrome c mimicked function of the mitochondrial apoptosis-induced channel MAC and caused apoptosis of both target and nearby osteoblasts. This effect was suppressed by inhibiting gap junction intercellular communication. A bystander effect was also observed after exogenous expression of tBid, which facilitates MAC formation and cytochrome c release. Interestingly, in connexin-43 deficient osteoblasts, microinjection of cytochrome c induced apoptosis only in the target cell. These findings indicate that a death signal was generated downstream of MAC function and was transmitted through gap junctions to amplify apoptosis in neighboring cells. This concept may have implications in development of new therapeutic approaches. 相似文献
59.
Mina Song Jae Eun Park Sung Goo Park Hyung-Kyoon Choi Seong Eon Ryu Sayeon Cho 《Biochemical and biophysical research communications》2009,381(4):491-6837
Protein phosphorylation plays critical roles in many regulatory mechanisms controlling cell activities and thus involved in various diseases. The cellular equilibrium of phosphorylation is regulated through the actions of protein kinases and phosphatases. Therefore, these regulatory proteins have emerged as promising targets for drug development. In this study, we screened protein tyrosine phosphatases (PTPs) by in vitro phosphatase assays to identify PTPs that are inhibited by 8-hydroxy-7-(6-sulfonaphthalen-2-yl)diazenyl-quinoline-5-sulfonic acid (NSC-87877), a potent inhibitor of SHP-1 and SHP-2 PTPs. Phosphatase activity of dual-specificity protein phosphatase 26 (DUSP26) was decreased by the inhibitor in a dose-dependent manner. Kinetic studies with NSC-87877 and DUSP26 revealed a competitive inhibition. NSC-87877 effectively inhibited DUSP26-mediated dephosphorylation of p38, a member of mitogen-activated protein kinase (MAPK) family. Since DUSP26 is involved in survival of anaplastic thyroid cancer (ATC) cells, NSC-87877 could be a therapeutic reagent for treating ATC. 相似文献
60.
Heui-Young Ryu Jiseon Lee Sanghwa Yang Haein Park Sojoong Choi Kyeong-Cheon Jung Seung-Taek Lee Je-Kyung Seong Inn-Oc Han Eok-Soo Oh 《The Journal of biological chemistry》2009,284(51):35692-35701
Although elevated syndecan-2 expression is known to be crucial for the tumorigenic activity in colon carcinoma cells, how syndecan-2 regulates colon cancer is unclear. In human colon adenocarcinoma tissue samples, we found that both mRNA and protein expression of syndecan-2 were increased, compared with the neighboring normal epithelium, suggesting that syndecan-2 plays functional roles in human colon cancer cells. Consistent with this notion, syndecan-2-overexpressing HT-29 colon adenocarcinoma cells showed enhanced migration/invasion, anchorage-independent growth, and primary tumor formation in nude mice, paralleling their morphological changes into highly tumorigenic cells. In addition, our experiments revealed that syndecan-2 enhanced both expression and secretion of matrix metalloproteinase-7 (MMP-7), directly interacted with pro-MMP-7, and potentiated the enzymatic activity of pro-MMP-7 by activating its processing into the active MMP-7. Collectively, these data strongly suggest that syndecan-2 functions as a docking receptor for pro-MMP-7 in colon cancer cells. 相似文献