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131.
Huang J Hamasaki T Ozoe F Ohta H Enomoto K Kataoka H Sawa Y Hirota A Ozoe Y 《Biochemistry》2007,46(20):5896-5903
Octopamine (OA) is a biogenic amine with a widespread distribution in the insect nervous system. OA modulates and/or regulates various behavioral patterns of insects as a neurotransmitter, neuromodulator, and neurohormone. OA receptors (OARs) belong to one of the families of G protein-coupled receptors (GPCRs). The binding of OA to OARs is coupled to the activation of the specific G proteins, which induces the release of intracellular second messengers such as cAMP and/or calcium. We previously reported the isolation of an OAR (BmOAR1) from Bombyx mori. In the study presented here, five mutated BmOAR1s were constructed with a point mutation in the putative binding crevice and expressed in HEK-293 cells. The S202A mutant receptor was found to retain the cAMP response to OA as does the wild-type receptor, but such function was impaired in the other four mutants (D103A, S198A, Y412F, and S198A/S202A). Furthermore, competition binding assays using [3H]OA and calcium mobilization assays gave results that were approximately consistent with those of the cAMP assays. Taken together, the results indicate that D103 and S198 are involved in the binding and activation of BmOAR1 with OA through electrostatic or hydrogen bond interactions, but S202 does not appear to participate in this process. Y412 seems to be involved in one of the active forms of BmOAR1. These findings should prove helpful in designing new pest control chemicals. 相似文献
132.
The plant pathogen Pantoea ananatis produces N-acylhomoserine lactone and causes center rot disease of onion by quorum sensing 下载免费PDF全文
Morohoshi T Nakamura Y Yamazaki G Ishida A Kato N Ikeda T 《Journal of bacteriology》2007,189(22):8333-8338
A number of gram-negative bacteria have a quorum-sensing system and produce N-acyl-l-homoserine lactone (AHL) that they use them as a quorum-sensing signal molecule. Pantoea ananatis is reported as a common colonist of wheat heads at ripening and causes center rot of onion. In this study, we demonstrated that P. ananatis SK-1 produced two AHLs, N-hexanoyl-l-homoserine lactone (C6-HSL) and N-(3-oxohexanoyl)-l-homoserine lactone (3-oxo-C6-HSL). We cloned the AHL-synthase gene (eanI) and AHL-receptor gene (eanR) and revealed that the deduced amino acid sequence of EanI/EanR showed high identity to those of EsaI/EsaR from P. stewartii. EanR repressed the ean box sequence and the addition of AHLs resulted in derepression of ean box. Inactivation of the chromosomal eanI gene in SK-1 caused disruption of exopolysaccharide (EPS) biosynthesis, biofilm formation, and infection of onion leaves, which were recovered by adding exogenous 3-oxo-C6-HSL. These results demonstrated that the quorum-sensing system involved the biosynthesis of EPS, biofilm formation, and infection of onion leaves in P. ananatis SK-1. 相似文献
133.
We propose a multiple comparison procedure to identify the minimum effective dose level by sequentially comparing each dose level with the zero dose level in the dose finding test. If we can find the minimum effective dose level at an early stage in the sequential test, it is possible to terminate the procedure in the dose finding test after a few group observations up to the dose level. Thus, the procedure is viable from an economical point of view when high costs are involved in obtaining the observations. In the procedure, we present an integral formula to determine the critical values for satisfying a predefined type I familywise error rate. Furthermore, we show how to determine the required sample size in order to guarantee the power of the test in the procedure. In practice, we compare the power of the test and the required sample size for various configurations of the population means in simulation studies and adopt our sequential procedure to the dose response test in a case study. 相似文献
134.
Shibamoto T Shimo T Cui S Zhang W Takano H Kurata Y Tsuchida H 《American journal of physiology. Regulatory, integrative and comparative physiology》2007,293(6):R2202-R2209
Mast cells and other cells such as macrophages have been shown to mediate systemic anaphylaxis. We determined the roles of mast cells and Kupffer cells in hepatic and systemic anaphylaxis of rats. Roles of mast cells were examined by using the mast cell-deficient white spotting (Ws/Ws) rat; the Ws/Ws and wild type (+/+) rats were sensitized with ovalbumin (1 mg). Roles of Kupffer cells were examined by depleting Kupffer cells using gadolinium chloride or liposome-encapsulated dichloromethylene diphosphonate in the Ws/Ws and Sprague-Dawley rats. An intravenous injection of 0.6 mg ovalbumin caused substantial anaphylactic hypotension in both the Ws/Ws and +/+ rats; however, the occurrence was delayed in the Ws/Ws rats. After antigen, portal venous pressure increased by 13.1 cmH2O in the +/+ rats, while it increased only by 5.7 cmH2O in the Ws/Ws rats. In response to antigen, the isolated perfused liver of the Ws/Ws rats also showed weak venoconstriction, the magnitude of which was one tenth as large as that of the +/+ rats, indicating that hepatic anaphylaxis was primarily due to mast cells. In contrast, Kupffer cell depletion did not attenuate anaphylactic hepatic venoconstriction in isolated perfused livers. In conclusion, mast cells are involved mainly in anaphylactic hepatic presinusoidal portal venoconstriction but only in the early stage of anaphylactic systemic hypotension in rats. Macrophages, including Kupffer cells, do not participate in rat hepatic anaphylactic venoconstriction. 相似文献
135.
Horio T Hamasaki T Inoue T Wakayama T Itou S Naito H Asaki T Hayase H Niwa T 《Bioorganic & medicinal chemistry letters》2007,17(10):2712-2717
To investigate why 3-substituted benzamide derivatives show dual inhibition of Abl and Lyn protein tyrosine kinases, we determined their inhibitory activities against Abl and Lyn, carried out molecular modeling, and conducted a structure-activity relationship study with the aid of a newly determined X-ray structure of the Abl/Lyn dual inhibitor INNO-406 (formerly known as NS-187) bound to human Abl. We found that this series of compounds interacted with both kinases in very similar ways, so that they can inhibit both kinases effectively. 相似文献
136.
Marcotullio MC Pagiotti R Maltese F Oball-Mond Mwankie GN Hoshino T Obara Y Nakahata N 《Bioorganic & medicinal chemistry》2007,15(8):2878-2882
Two new cyathane diterpenes, cyrneine C (4) and D (5), were isolated from the mushroom Sarcodon cyrneus, along with previously isolated cyrneine A, B and glaucopine C. The structures of the novel diterpenoids were determined by the analysis of spectroscopic data. Effects of the cyrneines and glaucopine C on the NGF gene expression in 1321N1 cells and on neurite outgrowth on PC12 cells were evaluated. 相似文献
137.
138.
Sakashita H Akahoshi F Yoshida T Kitajima H Hayashi Y Ishii S Takashina Y Tsutsumiuchi R Ono S 《Bioorganic & medicinal chemistry》2007,15(2):641-655
Dipeptidyl peptidase IV (DPP-IV) inhibitors are looked to as a potential new antidiabetic agent class. A series of [(S)-gamma-(arylamino)prolyl]thiazolidine compounds in which the electrophilic nitrile is removed are chemically stable DPP-IV inhibitors. To discover a structure for the gamma-substituent of the proline moiety more suitable for interacting with the S(2) pocket of DPP-IV, optimization focused on the gamma-substituent was carried out. The indoline compound 22e showed a DPP-IV-inhibitory activity 100-fold more potent than that of the prolylthiazolidine 10 and comparable to that of NVP-DPP728. It also displayed improved inhibitory selectivity for DPP-IV over DPP8 and DPP9 compared to compound 10. Indoline compounds such as 22e have a rigid conformation with double restriction of the aromatic moiety by proline and indoline structures to promote interaction with the binding site in the S(2) pocket of DPP-IV. The double restriction effect provides a potent inhibitory activity which compensates for the decrease in activity caused by removing the electrophilic nitrile. 相似文献
139.
TRPM7 is a stretch- and swelling-activated cation channel involved in volume regulation in human epithelial cells 总被引:6,自引:0,他引:6
Stretch- and swelling-activated cation (SSAC) channels play essential roles not only in sensing and transducing external mechanical stresses but also in regulating cell volume in living cells. However, the molecular nature of the SSAC channel has not been clarified. In human epithelial HeLa cells, single-channel recordings in cell-attached and inside-out patches revealed expression of a Mg2+- and Gd3+-sensitive nonselective cation channel that is exquisitely sensitive to membrane stretch. Whole cell recordings revealed that the macroscopic cationic currents exhibit transient receptor potential (TRP) melastatin (TRPM)7-like properties such as outward rectification and sensitivity to Mg2+ and Gd3+. The whole cell cation current was augmented by osmotic cell swelling. RT-PCR and Western blotting demonstrated molecular expression of TRPM7 in HeLa cells. Treatment with small interfering RNA (siRNA) targeted against TRPM7 led to abolition of single stretch-activated cation channel currents and of swelling-activated, whole cell cation currents in HeLa cells. The silencing of TRPM7 by siRNA reduced the rate of cell volume recovery after osmotic swelling. A similar inhibition of regulatory volume decrease was also observed when extracellular Ca2+ was removed or Gd3+ was applied. It is thus concluded that TRPM7 represents the SSAC channel endogenously expressed in HeLa cells and that, by serving as a swelling-induced Ca2+ influx pathway, it plays an important role in cell volume regulation. regulatory volume decrease 相似文献
140.
C-reactive protein suppresses insulin signaling in endothelial cells: role of spleen tyrosine kinase
Although few epidemiological studies have demonstrated that C-reactive protein (CRP) is related to insulin resistance, no study to date has examined the molecular mechanism. Here, we show that recombinant CRP attenuates insulin signaling through the regulation of spleen tyrosine kinase (Syk) on small G-protein RhoA, jun N-terminal kinase (JNK) MAPK, insulin receptor substrate-1 (IRS-1), and endothelial nitric oxide synthase in vascular endothelial cells. Recombinant CRP suppressed insulin-induced NO production, inhibited the phosphorylation of Akt and endothelial nitric oxide synthase, and stimulated the phosphorylation of IRS-1 at the Ser307 site in a dose-dependent manner. These events were blocked by treatment with an inhibitor of RhoA-dependent kinase Y27632, or an inhibitor of JNK SP600125, or the transfection of dominant negative RhoA cDNA. Next, anti-CD64 Fcgamma phagocytic receptor I (FcgammaRI), but not anti-CD16 (FcgammaRIIIa) or anti-CD32 (FcgammaRII) antibody, partially blocked the recombinant CRP-induced phosphorylation of JNK and IRS-1 and restored, to a certain extent, the insulin-stimulated phosphorylation of Akt. Furthermore, we identified that recombinant CRP modulates the phosphorylation of Syk tyrosine kinase in endothelial cells. Piceatannol, an inhibitor of Syk tyrosine kinase, or infection of Syk small interference RNA blocked the recombinant CRP-induced RhoA activity and the phosphorylation of JNK and IRS-1. In addition, piceatannol also restrained CRP-induced endothelin-1 production. We conclude that recombinant CRP induces endothelial insulin resistance and dysfunction, and propose a new mechanism by which recombinant CRP induces the phosphorylation of JNK and IRS-1 at the Ser307 site through a Syk tyrosine kinase and RhoA-activation signaling pathway. 相似文献