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101.
Toll-like receptor (TLR) 2 and TLR5, but not TLR4, are required for Helicobacter pylori-induced NF-kappa B activation and chemokine expression by epithelial cells 总被引:11,自引:0,他引:11
Smith MF Mitchell A Li G Ding S Fitzmaurice AM Ryan K Crowe S Goldberg JB 《The Journal of biological chemistry》2003,278(35):32552-32560
102.
The discovery of potent, selective, and orally bioavailable hNK1 antagonists derived from pyrrolidine 总被引:2,自引:0,他引:2
Lin P Chang L Devita RJ Young JR Eid R Tong X Zheng S Ball RG Tsou NN Chicchi GG Kurtz MM Tsao KL Wheeldon A Carlson EJ Eng W Burns HD Hargreaves RJ Mills SG 《Bioorganic & medicinal chemistry letters》2007,17(18):5191-5198
SAR studies on amides, ureas, and vinylogous amides derived from pyrrolidine led to the discovery of several potent hNK(1) antagonists. One particular vinylogous amide (45b) had excellent potency, selectivity, pharmacokinetic profile, and functional activity in vivo. An in vivo rhesus macaque brain receptor occupancy PET study for compound 45b revealed an estimated Occ(90) approximately 300 ng/ml. 相似文献
103.
Kim TY Shin SK Song MY Lee JE Park KS 《Biochemical and biophysical research communications》2012,417(3):1030-1034
Transient receptor potential melastatin 7 (TRPM7) channels are divalent cation-selective ion channels that are permeable to Ca(2+) and Mg(2+). TRPM7 is ubiquitously expressed in vertebrate cells and contains both an ion channel and a kinase domain. TRPM7 plays an important role in regulating cellular homeostatic levels of Ca(2+) and Mg(2+) in mammalian cells. Although studies have shown that the kinase domain of TRPM7 is required for channel activation and can phosphorylate other target proteins, a systematic analysis of intact TRPM7 channel phosphorylation sites expressed in mammalian cells is lacking. We applied mass spectrometric proteomic techniques to identify and characterize the key phosphorylation sites in TRPM7 channels. We identified 14 phosphorylation sites in the cytoplasmic domain of TRPM7, eight of which have not been previously reported. The identification of phosphorylation sites using antibody-based immunopurification and mass spectrometry is an effective approach for defining the phosphorylation status of TRPM7 channels. The present results show that TRPM7 channels are phosphorylated at multiple sites, which serves as a mechanism to modulate the dynamic functions of TRPM7 channels in mammalian cells. 相似文献
104.
Activation of Toll-like receptor 4 is associated with insulin resistance in adipocytes 总被引:3,自引:0,他引:3
Song MJ Kim KH Yoon JM Kim JB 《Biochemical and biophysical research communications》2006,346(3):739-745
Chronic inflammation is closely associated with metabolic disorders such as obesity and type 2 diabetes, however, the underlying mechanism is unclear. Toll-like receptors (TLRs) play a key role in innate immune response as well as inflammatory signals. Here, we observed that mRNA level of TLR4 was induced during adipocyte differentiation and remarkably enhanced in fat tissues of obese db/db mice. In addition, activation of TLR4 with either LPS or free fatty acids stimulated NFkappaB signaling and expression of inflammatory cytokine genes, such as TNFalpha and IL-6 in 3T3-L1 adipocytes. Furthermore, we discovered that TLR4 activation in 3T3-L1 adipocytes provoked insulin resistance. Taken together, these results suggest that activation of TLR4 in adipocyte might be implicated in the onset of insulin resistance in obesity and type 2 diabetes. 相似文献
105.
双探针原位杂交揭示稻属BB、cc 和EE基因组之间的分化
李常宝1 张大明1* 葛颂1 卢宝荣2 洪德元1 相似文献
106.
从江浙蝮蛇中分离纯化的碱性磷脂酶A2在pH9.5,0.05mmol/LCHES缓冲液中,用汽相悬滴扩散的方法,获得了适用于高分辨率X射线结构分析的单晶.经X200B面探测器分析,表明该晶体属于正交晶系,P2I2I2I空间群,晶胞参数为a=97.13,b=103.69,c=23.27.并收集了一套衍射数据,独立衍射点数12001个,数据完整度为86.2%,Rmerge为0.0459.最高分辨率达2.0,根据分子量与晶胞体积估算,一个不对称单位含两个分子. 相似文献
107.
Ubiquitin-like modifications are macromolecular chemistry for which our understanding of the enzymatic mechanisms is lacking. Most E3 ligases in ubiquitin-like modifications do not directly participate in chemistry but are thought to confer allosteric effects; however, the nature of the allosteric effects has been elusive. Recent molecular dynamics simulations suggested that an E3 binding enhances the population of the conformational states of the E2·SUMO thioester that favor reactions. In this study, we conducted the first temperature-dependent enzyme kinetic analysis to investigate the role of an E3 on activation entropy and enthalpy. The small ubiquitin-like modifier (SUMO) E3, RanBP2, confers unusually large, favorable activation entropy to lower the activation energy of the reaction. Mutants of RanBP2, designed to alter the flexibilities of the E2·SUMO thioester, showed a direct correlation of their favorable entropic effects with their ability to restrict the conformational flexibility of the E2·SUMO thioester. While the more favorable activation entropy is consistent with the previously suggested role of E3 in conformational selection, the large positive entropy suggests a significant role of solvent in catalysis. Indeed, molecular dynamics simulations in explicit water revealed that the more stable E2·SUMO thioester upon E3 binding results in stabilization of a large number of bound water molecules. Liberating such structured water at the transition state can result in large favorable activation entropy but unfavorable activation enthalpy. The entropy-driven mechanism of the E3 is consistent with the lack of structural conservation among E3s despite their similar functions. This study also illustrates how proteins that bind both SUMO and E2 can function as E3s and how intrinsically unstructured proteins can enhance macromolecular chemistry in addition to their known advantages in protein--protein interactions. 相似文献
108.
Effects of culture conditions on osteogenic differentiation in human mesenchymal stem cells 总被引:1,自引:0,他引:1
Song SJ Jeon O Yang HS Han DK Kim BS 《Journal of microbiology and biotechnology》2007,17(7):1113-1119
Human bone marrow-derived mesenchymal stem cells (hBMMSCs) must differentiate into osteogenic cells to allow for successful bone regeneration. In this study, we investigated the effects of different combinations of three soluble osteogenic differentiation-inducing factors [L-ascorbic acid (AC), beta-glycerophosphate (betaG), and bone morphogenic protein-2 (BMP-2)] and the presence of a hydroxyapatite (HA) substrate on hBMMSC osteogenic differentiation in vitro. hBMMSCs were cultured in medium containing various combinations of the soluble factors on culture plates with or without HA coating. After 7 days of culture, alkaline phosphatase (ALP) activity, calcium deposition, and osteoprotegerin (OPG) and osteopontin (OPN) expression were measured. The effects of individual and combined factors were evaluated using a factorial analysis method. BMP-2 predominantly affected expression of early markers of osteogenic differentiation (ALP and OPG). HA had the highest positive effect on OPN expression and calcium deposition. The interaction between AC, betaG, and HA had the second highest positive effect on ALP activity. 相似文献
109.
HIV-1 TAT-mediated protein transduction and subcellular localization using novel expression vectors 总被引:7,自引:0,他引:7
Several novel prokaryotic and eukaryotic expression vectors were constructed for protein transduction and subcellular localization. These vectors employed an N-terminal stretch of 11 basic amino acid residues (47-57) from the human immunodeficiency virus type 1 (HIV-1) TAT protein transduction domain (PTD) for protein translocation and cellular localization. The vectors also contained a six-histidine (His(6)) tag at the N- or C-terminus for convenient purification and detection, and a multiple cloning site for easy insertion of foreign genes. Some heterologous genes including HSV-TK, Bcl-rambo, Smac/DIABLO and GFP were fused in-frame to TAT PTD and successfully overexpressed in Escherichia coli. The purified TAT-GFP fusion protein was able to transduce into the mammalian cells and was found to locate mainly in the cytosol when exogenously added to the cell culture medium. However, using a transfection system, mammalian-expressed TAT-GFP predominantly displayed a nuclear localization and nucleolar accumulation in mammalian cell lines. This discrepancy implies that the exact subcellular localization of transduced protein may depend on cell type, the nature of imported proteins and delivery approach. Taken together, our results demonstrate that a TAT PTD length of 11 amino acids was sufficient to confer protein internalization and its subsequent cellular localization. These novel properties allow these vectors to be useful for studying protein transduction and nuclear import. 相似文献
110.
目的 探讨结核杆菌感染与恶性肿瘤的关系。方法 采用多聚酶链反应(PCR) 技术检测两种恶性肿瘤组织中结核杆菌DNA(TB- DNA) 。结果41 例恶性肿瘤组织中检出TB- DNA 阳性患者8 例,占19.5 % ,且TB-DNA 阳性患者肿瘤发病部位基本与结核病的好发部位一致。结论 结核杆菌感染可能与一些恶性肿瘤存在特殊相关性。 相似文献