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991.
Kawai M Ando K Matsumoto Y Sakurada I Hirota M Nakamura H Ohta A Sudo M Hattori K Takashima T Hizue M Watanabe S Fujita I Mizutani M Kawamura M 《Bioorganic & medicinal chemistry letters》2007,17(20):5558-5562
(-)-6-[2-[4-(3-Fluorophenyl)-4-hydroxy-1-piperidinyl]-1-hydroxyethyl]-3,4-dihydro-2(1H)-quinolinone was identified as an orally active NR2B-subunit selective N-methyl-d-aspartate (NMDA) receptor antagonist. It has very high selectivity for NR2B subunits containing NMDA receptors versus the HERG-channel inhibition (therapeutic index=4200 vs NR2B binding IC(50)). This compound has improved pharmacokinetic properties compared to the prototype CP-101,606. 相似文献
992.
Nakagawa-Goto K Nakamura S Bastow KF Nyarko A Peng CY Lee FY Lee FC Lee KH 《Bioorganic & medicinal chemistry letters》2007,17(10):2894-2898
Sixteen different taxoid conjugates were prepared by linking various anticancer compounds, including camptothecin (CPT), epipodophyllotoxin (EP), colchicine (COL), and glycyrrhetinic acid (GA), at the 2'- or 7-position on paclitaxel (TXL, 1) through an ester, imine, amine, or amide bond. Newly synthesized conjugates were evaluated for cytotoxic activity against replication of several human tumor cell lines. Among them, TXL-CPT conjugates, 8-10, were more potent than TXL itself against the human prostate carcinoma cell line PC-3 (ED(50)=14.8, 3.1, 19.4nM compared with 55.5nM), and conjugate 10 was also 8-fold more active than TXL against the LN-CAP prostate cancer cell line. These compounds also possessed anti-angiogenesis ability as well as lower inhibitory effects against a normal cell line (MRC-5). Thus, conjugates 8-10 are possible antitumor drug candidates, particularly for prostate cancer. 相似文献
993.
Aoi W Naito Y Nakamura T Akagiri S Masuyama A Takano T Mizushima K Yoshikawa T 《The Journal of nutritional biochemistry》2007,18(2):140-145
Milk fermented with a starter containing Lactobacillus helveticus and Saccharomyces cerevisiae is drunk on a daily basis by many people in Japan and has several beneficial effects. We studied the influence of this fermented milk product on muscle damage after prolonged exercise in rats. Wistar rats were divided into four groups: rested controls, rested rats given fermented milk diet, exercised rats and exercised rats given fermented milk diet. After 3 weeks of acclimatization, both exercise groups were made to run on a treadmill at 26 m/min for 60 min. Exercise increased the serum creatine kinase level, as well as myeloperoxidase activity and the level of thiobarbituric-acid-reactive substances in the gastrocnemius muscle after 24 h. These changes were ameliorated by intake of fermented milk. An increase of CINC-1 was also ameliorated by fermented milk. Furthermore, milk diet increased the mRNA and protein levels of protective proteins such as antioxidants and chaperone proteins. These results indicate that fermented milk can ameliorate delayed-onset muscle damage after prolonged exercise, which is associated with an increased antioxidant capacity of muscles. 相似文献
994.
Ingebrandt S Han Y Nakamura F Poghossian A Schöning MJ Offenhäusser A 《Biosensors & bioelectronics》2007,22(12):2834-2840
We present a label-free method for the detection of DNA hybridization, which is monitored by non-metallized silicon field-effect transistors (FET) in a microarray approach. The described method enables a fast and fully electronic readout of ex situ binding assays. The label-free detection utilizing the field-effect is based on the intrinsic charge of the DNA molecules and/or on changes of the solid–liquid interface impedance, when biomolecules bind to the sensor surface. With our sensor system, usually a time-resolved, dc readout is used. In general, this FET signal suffers from sensor drift, temperature drift, changes in electrolyte composition or pH value, influence of the reference electrode, etc. In this article, we present a differential ac readout concept for FET microarrays, which enables a stable operation of the sensor against many of these side-parameters, reliable readout and a possibility for a quick screening of large sensor arrays. We present the detection of point mutations in short DNA samples with this method in an ex situ binding assay. 相似文献
995.
Miyanishi N Nishi N Abe H Kashio Y Shinonaga R Nakakita S Sumiyoshi W Yamauchi A Nakamura T Hirashima M Hirabayashi J 《Glycobiology》2007,17(4):423-432
Galectin-9 (Gal-9) is a tandem-repeat-type member of the galectin family associated with diverse biological processes, such as apoptosis, cell aggregation, and eosinophil chemoattraction. Although the detailed sugar-binding specificity of Gal-9 has been elucidated, molecular mechanisms that underlie these functions remain to be investigated. During the course of our binding study by affinity chromatography and surface plasmon resonance (SPR) analysis, we found that human Gal-9 interacts with immobilized Gal-9 in the protein-protein interaction mode. Interestingly, this intermolecular interaction strongly depended on the activity of the carbohydrate recognition domain (CRD), because the addition of potent saccharide inhibitors abolished the binding. The presence of multimers was also confirmed by Ferguson plot analysis of result of polyacrylamide gel electrophoresis and matrix-assisted laser-desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry (MS). Moreover, this intermolecular interaction was observed between Gal-9 and other galectin members, such as Gal-3 and Gal-8, but not Gal-1. Because such properties have not been reported yet, they may explain an unidentified mechanism underlying the diverse functions of Gal-9. 相似文献
996.
Kojima H Suzuki T Kato T Enomoto K Sato S Kato T Tabata S Sáez-Vasquez J Echeverría M Nakagawa T Ishiguro S Nakamura K 《The Plant journal : for cell and molecular biology》2007,49(6):1053-1063
Animal and yeast nucleolin function as global regulators of ribosome synthesis, and their expression is tightly linked to cell proliferation. Although Arabidopsis contains two genes for nucleolin, AtNuc-L1 is the predominant if not only form of the protein found in most tissues, and GFP-AtNuc-L1 fusion proteins were targeted to the nucleolus. Expression of AtNuc-L1 was strongly induced by sucrose or glucose but not by non-metabolizable mannitol or 2-deoxyglucose. Sucrose also caused enhanced expression of genes for subunits of C/D and H/ACA small nucleolar ribonucleoproteins, as well as a large number of genes for ribosomal proteins (RPs), suggesting that carbohydrate availability regulates de novo ribosome synthesis. In sugar-starved cells, induction of AtNuc-L1 occurred with 10 mM glucose, which seemed to be a prerequisite for resumption of growth. Disruption of AtNuc-L1 caused an increased steady-state level of pre-rRNA relative to mature 25S rRNA, and resulted in various phenotypes that overlap those reported for several RP gene mutants, including a reduced growth rate, prolonged lifetime, bushy growth, pointed leaf, and defective vascular patterns and pod development. These results suggest that the rate of ribosome synthesis in the meristem has a strong impact not only on the growth but also the structure of plants. The AtNuc-L1 disruptant exhibited significantly reduced sugar-induced expression of RP genes, suggesting that AtNuc-L1 is involved in the sugar-inducible expression of RP genes. 相似文献
997.
Antitumor agents. 258. Syntheses and evaluation of dietary antioxidant--taxoid conjugates as novel cytotoxic agents 总被引:1,自引:0,他引:1
Nakagawa-Goto K Yamada K Nakamura S Chen TH Chiang PC Bastow KF Wang SC Spohn B Hung MC Lee FY Lee FC Lee KH 《Bioorganic & medicinal chemistry letters》2007,17(18):5204-5209
Various dietary antioxidants, including vitamins, flavonoids, curcumin, and a coumarin, were conjugated with paclitaxel (1) through an ester linkage. The newly synthesized compounds were evaluated for cytotoxic activity against several human tumor cell lines as well as the corresponding normal cell lines. Interestingly, most tested conjugates selectively inhibited the growth of 1A9 (ovarian) and KB (nasopharyngeal) tumor cells without activity against other cell lines. Particularly, conjugates 16 and 20 were highly active against 1A9 (ED(50) value of 0.005 microg/mL) as well as KB (ED(50) values of 0.005 and 0.14 microg/mL, respectively) cells. Compound 22b, the glycinate ester salt of vitamin E conjugated with 1, appears to be a promising lead for further development as a clinical trial candidate as it exhibited strong inhibitory activity against Panc-1 (pancreatic cancer) with less effect on the related E6E7 (normal) cell line. 相似文献
998.
Namiki K Nakamura A Furuya M Mizuhashi S Matsuo Y Tokuhara N Sudo T Hama H Kuwaki T Yano S Kimura S Kasuya Y 《Journal of receptor and signal transduction research》2007,27(2-3):99-111
We investigated how p38alpha mitogen-activated protein kinase (p38) is related to kainate-induced epilepsy and neuronal damages, by using the mice with a single copy disruption of the p38 alpha gene (p38alpha(+/-)). Mortality rate and seizure score of p38alpha(+/-) mice administered with kainate were significantly reduced compared with the case of wild-type (WT) mice. This was clearly supported by the electroencephalography data in which kainate-induced seizure duration and frequency in the brain of p38alpha(+/-) mice were significantly suppressed compared to those of WT mice. As a consequence of seizure, kainate induced delayed neuronal damages in parallel with astrocytic growth in the hippocampus and ectopic innervation of the mossy fibers into the stratum oriens in the CA3 region of hippocampus in WT mice, whose changes were moderate in p38alpha(+/-) mice. Likewise, kainate-induced phosphorylation of calcium/calmodulin-dependent kinase II in the hippocampus of p38alpha (+/-) mice was significantly decreased compared to that of WT mice. These results suggest that p38alpha signaling pathway plays an important role in epileptic seizure and excitotoxicity. 相似文献
999.
BACKGROUND: Helicobacter pylori mainly inhabit the mucus layer in the gastric mucosa. However, mechanisms involving H. pylori colonization and proliferation in gastric mucosa are not well established. This study focuses on elucidating the role of gastric mucosal cells on growth of H. pylori. MATERIALS AND METHODS: H. pylori was co-cultured with the murine gastric surface mucosal cells (GSM06), and the growth of H. pylori on the cells was assessed by enumerating the colony-forming units (CFU). The H. pylori growth factor in the culture media conditioned by GSM06 cell was purified by HPLC, and the chemical structure of the growth factor was identified by analyses of (1)H- and (13)C-NMR spectra. RESULTS: A marked increase in the number of CFU of H. pylori was observed in the GSM06 cells. The enhanced H. pylori growth was also observed when indirectly incubated with GSM06 cells through semi-permeable membrane. In addition, culture media conditioned by GSM06 cell stimulated H. pylori growth approximately one thousand-fold. By bioassay-guided purification, the H. pylori growth factor was isolated from the conditioned medium of GSM06 cells and identified as L-lactic acid. The H. pylori growth-enhancing activity under microaerobic condition was well correlated with L-lactic acid concentrations in the conditioned media. CONCLUSIONS: This study demonstrates that L-lactic acid secreted by gastric mucosal cells enhances the growth of H. pylori, and this L-lactic acid-dependent growth of H. pylori may be important to the long-term colonization of H. pylori in the stomach. 相似文献
1000.
Yuasa HJ Hasegawa T Nakamura T Suzuki T 《Comparative biochemistry and physiology. Part B, Biochemistry & molecular biology》2007,146(4):461-469
The indoleamine 2,3-dioxygenase (IDO)-like myoglobin (Mb) is a unique type of Mb isolated from the buccal mass of several archgastropod species. Here, we expressed Sulculus diversicolor IDO-like Mb as a GST-fusion protein in bacteria. The visible spectrum of GST-fusion IDO-like Mb shows characteristic α- and β-peaks, indicating that it binds oxygen. To identify residues important in heme and oxygen binding, we constructed site-directed mutants. We initially replaced each of the 7 histidines of S. diversicolor IDO-like Mb with alanine. The spectra of three mutants (H74A, H288A, and H332A) revealed a remarkable loss of absorbance around 414 nm, indicating that they cannot bind heme. His74, His288, and His332 were also replaced by arginine or tyrosine. Neither H332R nor H332Y contains heme, suggesting that His332 is the proximal ligand of IDO-like Mb. In contrast, both H74R and H288Y mutants were isolated in the heme-binding oxy-form. The autoxidation rates of these two mutants showed that they can bind oxygen as stably as wild-type. His74 and His288 might be partially associated with heme-binding, but do not act as the distal ligand. The S. diversicolor IDO-like Mb seems to stably bind oxygen in a different manner from normal myoglobins. 相似文献