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991.
FlhA is an integral membrane component of the Salmonella type III flagellar protein export apparatus. It consists of 692 amino acid residues and has two domains: the N-terminal transmembrane domain consisting of the first 327 amino acid residues, and the C-terminal cytoplasmic domain (FlhAC) comprising the remainder. Here, we have investigated the structure and function of FlhAC. DNA sequence analysis revealed that temperature-sensitive flhA mutations, which abolish flagellar protein export at the restrictive temperature, lie in FlhAC, indicating that FlhAC plays an important role in the protein export process. Limited proteolysis of purified His-FlhAC by trypsin and V8 showed that only a small part of FlhAC near its N terminus (residues 328-351) is sensitive to proteolysis. FlhAC38K, the smallest fragment produced by V8 proteolysis, is monomeric and has a spherical shape as judged by analytical gel filtration chromatography and analytical ultracentrifugation. The far-UV CD spectrum of FlhAC38K showed that it contains considerable amounts of secondary structure. FlhA(Delta328-351) missing residues 328-351 failed to complement the flhA mutant, indicating that the proteolytically sensitive region of FlhA is important for its function. FlhA(Delta328-351) was inserted into the cytoplasmic membrane, and exerted a strong dominant negative effect on wild-type cells, suggesting that it retains the ability to interact with other export components within the cytoplasmic membrane. Overproduced FlhAC38K inhibited both motility and flagellar protein export of wild-type cells to some degree, suggesting that FlhAC38K is directly involved in the translocation reaction. Amino acid residues 328-351 of FlhA appear to be a relatively flexible linker between the transmembrane domain and FlhAC38K. 相似文献
992.
Receptor-activating peptides for PAR-1 and PAR-2 relax rat gastric artery via multiple mechanisms 总被引:2,自引:0,他引:2
Kawabata A Nakaya Y Ishiki T Kubo S Kuroda R Sekiguchi F Kawao N Nishikawa H Kawai K 《Life sciences》2004,75(22):2689-2702
Receptor-activating peptides for protease-activated receptors (PARs) 1 or 2 enhance gastric mucosal blood flow (GMBF) and protect against gastric mucosal injury in rats. We thus examined and characterized the effects of PAR-1 and PAR-2 agonists on the isometric tension in isolated rat gastric artery. The agonists for PAR-2 or PAR-1 produced vasodilation in the endothelium-intact arterial rings, which was abolished by removal of the endothelium. The mechanisms underlying the PAR-2- and PAR-1-mediated relaxation involved NO, endothelium-derived hyperpolarizing factor (EDHF) and prostanoids, to distinct extent, as evaluated by use of inhibitors of NO synthase, cyclo-oxygenase and Ca2+-activated K+ channels. The EDHF-dependent relaxation responses were significantly attenuated by gap junction inhibitors. These findings demonstrate that endothelial PAR-1 and PAR-2, upon activation, dilate the gastric artery via NO and prostanoid formation and also EDHF mechanisms including gap junctions, which would enhance GMBF. 相似文献
993.
Yama S Nishioka W Hirokami Y Setoguchi R Takeyama N Saeki K Matsumoto Y Hayashi T Doi K Onodera T 《Microbiology and immunology》2004,48(1):7-13
The effects of tacrolimus on insulin-dependent diabetes mellitus (IDDM) induced by the D-variant of encephalomyocarditis virus (D-EMCV) have been investigated. Male BALB/c mice were treated with tacrolimus before viral inoculation, and then were inoculated with 10 plaque forming units (PFU) of DEMCV. The mice continued to be treated with tacrolimus until the animals were sacrificed. D-EMCV-infected mice, which were treated with saline as controls, showed abnormal glucose tolerance test (GTT) values, whereas all infected mice with tacrolimus pretreatment were normal on 7 days-post inoculation (DPI). Histological observations revealed that non-treated tacrolimus D-EMCV-infected mice and which developed diabetes showed severe insulitis in their islets of Langerhans. On the other hand, D-EMCV-infected mice treated with tacrolimus were normal. In D-EMCV-infected mice, viruses in the pancreata were detected at the same level regardless of treatment with tacrolimus or saline. Expressions of TNF-alpha and IFN-gamma mRNA in spleens of tacrolimus-treated D-EMCV-infected mice were lower than that of non-treated tacrolimus DEMCV-infected mice on 7 DPI. The results suggest that tacrolimus suppresses expressions of TNF-alpha and IFN-gamma mRNAs to prevent the onset of D-EMCV-induced IDDM. 相似文献
994.
Galectin-9 in physiological and pathological conditions 总被引:8,自引:0,他引:8
Hirashima M Kashio Y Nishi N Yamauchi A Imaizumi TA Kageshita T Saita N Nakamura T 《Glycoconjugate journal》2004,19(7-9):593-600
We first cloned galectin-9 (Gal-9)/ecalectin as a T cell-derived eosinophil chemoattractant. Gal-9 plays a role in not only accumulation but also activation of eosinophils in experimental allergic models and human allergic patients, because Gal-9 induces eosinophil chemoattraction in vitro and in vivo and activates eosinophils in many aspects. Gal-9 requires divalent galactoside-binding activity but not the linker peptide of Gal-9 to exhibit its biological functions, and an unidentified matrix metalloproteinase is involved in the release of Gal-9. Our recent studies also showed that Gal-9 has other functions, such as cell differentiation, aggregation, adhesion, and death. Now, we and other groups are on the way of investigating the regulation and function of Gal-9 in a variety of physiological and pathological conditions. In this article, we will show the possible role of Gal-9 in physiological and pathological conditions by using our recent findings. 相似文献
995.
Tanaka M Itoh K Abe S Imai K Masuda T Koga R Itoh H Konomi Y Kinukawa N Sakata T 《Experimental biology and medicine (Maywood, N.J.)》2004,229(9):940-945
This study examined whether charting daily weight patterns can predict weight regain in obese patients. The subjects were 98 moderately obese Japanese women aged 23 to 66 years who were obliged to precisely record their daily weights during the initial 4-month education period, but not thereafter. The patients were followed up at 8, 12, and 16 months. Abdominal fat areas and blood samples were assessed in the outpatient clinic at 0, 4, and 16 months. The standard deviations (SDs) of the differences in body weight between "after waking up" and "after breakfast" (SDa), "after dinner" (SDb), and "before going to bed" (SDc) were calculated, which were parameters reflecting the fluctuations in the daily weight patterns during the first 4 months. SDc, but not SDa or SDb, was correlated positively with weight regain at 8, 12, and 16 months (P = 0.049, P = 0.002, and P = 0.001, respectively). There were significant differences in temporal change in body weight and abdominal visceral fat between the small SDc group (SDc =25th percentile) and the large SDc group (SDc >75th percentile), but not for subcutaneous abdominal fat or the serum concentrations of glucose, insulin, or lipids. The results indicate that fluctuation of body weight immediately before going to bed is useful for predicting the rebound in body weight. 相似文献
996.
Haginoya N Kobayashi S Komoriya S Hirokawa Y Furugori T Nagahara T 《Bioorganic & medicinal chemistry letters》2004,14(11):2935-2939
In our investigation of factor Xa inhibitors, a series of 1-(6-chloronaphthalen-2-yl)sulfonyl-4-(4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carbonyl)piperazines 3a-i were synthesized. In vitro inhibitory activities of the compounds against factor Xa and coagulation are summarized. Among the compounds, 3c and 3d, possessing a carbamoyl or N-methylcarbamoyl moiety, showed potent inhibitory activities when administered orally to rats. 相似文献
997.
Moree WJ Kataoka K Ramirez-Weinhouse MM Shiota T Imai M Sudo M Tsutsumi T Endo N Muroga Y Hada T Tanaka H Morita T Greene J Barnum D Saunders J Kato Y Myers PL Tarby CM 《Bioorganic & medicinal chemistry letters》2004,14(21):5413-5416
Structure-activity relationships (SAR) of a weakly active class of CCR2b inhibitors were utilized to initiate a lead evolution program employing the Drug Discovery Engine. Several alternative structural series have been discovered that display nanomolar activity in the CCR2b binding and CCR2b-mediated chemotaxis assays. 相似文献
998.
Taniguchi M Suzumura K Nagai K Kawasaki T Takasaki J Sekiguchi M Moritani Y Saito T Hayashi K Fujita S Tsukamoto S Suzuki K 《Bioorganic & medicinal chemistry》2004,12(12):3125-3133
The structure elucidation and biological activity of novel YM-254890 (1) analogues and semi-synthetic derivatives are described. Three natural analogues, YM-254891 (2), YM-254892 (3), and YM-280193 (4), were isolated from the fermentation broth of Chromobacterium sp. QS3666, and two hydrogenated derivatives, YM-385780 (5) and YM-385781 (6), were synthesized from YM-254890. Their structures were determined by one- and two-dimensional NMR studies and mass spectrometry. Among these compounds, two natural analogues 2-3 which possessed acyl groups at beta-HyLeu-1 and one derivative 6 whose conformation was similar to that of 1 showed comparable Galpha(q/11) inhibitory activity to that of 1. This indicates that the acyl beta-HyLeu residue plays an important role in activity and also that the alpha,beta-unsaturated carbonyl group of the N-MeDha residue is not critical to activity. The other hydrogenated derivative 5 had significantly less activity, which could be attributed to conformational differences. 相似文献
999.
Tamakoshi M Nakano Y Kakizawa S Yamagishi A Oshima T 《Extremophiles : life under extreme conditions》2001,5(1):17-22
A leuB strain of Thermus thermophilus TTY1, was transformed with a plasmid vector that directed expression of 3-isopropylmalate dehydrogenase (IPMDH) of Saccharomyces cerevisiae encoded by the LEU2 gene. The original strain could not grow at 50 degrees C without leucine, probably because of the low stability of S. cerevisiae IPMDH. The mutants that could grow without leucine were selected at 50 degrees, 60 degrees, 62 degrees, 65 degrees, 67 degrees, and 70 degrees C, step by step. All the mutant strains except for one isolated at 50 degrees C accumulated mutations. Mutations were serially accumulated: Glu255Val, Asn43Tyr, Ala62Thr, Asn110Lys, and Alal 12Val, respectively, at each step. The analyses of residual activity after heat treatment and the denaturation profile as monitored by circular dichroism showed that thermal stability was increased with accumulation of the mutations. The kinetic parameters of most mutant enzymes were similar to those of the wild type. However, some mutant enzymes showed a reverse correlation between stability and activity: the enzymes with a large increase in thermal stability showed lower activity. Although the wild-type enzyme is unstable in the absence of glycerol, the stabilizing effect of glycerol was not observed for all the mutant enzymes containing the Glu255Val substitution, which is assumed to be located at the hydrophobic interface between two subunits. 相似文献
1000.