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241.
Yuki Kawakami Shiori Hirano Mai Kinoshita Akemi Otsuki Toshiko Suzuki-Yamamoto Makiko Suzuki Masumi Kimoto Sae Sasabe Mitsuo Fukushima Koji Kishimoto Takashi Izumi Toru Oga Shuh Narumiya Mitsuaki Sugahara Masashi Miyano Shozo Yamamoto Yoshitaka Takahashi 《Biochimica et Biophysica Acta (BBA)/General Subjects》2014
Background
Cysteinyl leukotrienes (LTs) are key mediators in inflammation. To explore the structure of the antigen-recognition site of a monoclonal antibody against LTC4 (mAbLTC), we previously isolated full-length cDNAs for heavy and light chains of the antibody and prepared a single-chain antibody comprising variable regions of these two chains (scFvLTC).Methods
We examined whether mAbLTC and scFvLTC neutralized the biological activities of LTC4 and LTD4 by competing their binding to their receptors.Results
mAbLTC and scFvLTC inhibited their binding of LTC4 or LTD4 to CysLT1 receptor (CysLT1R) and CysLT2 receptor (CysLT2R) overexpressed in Chinese hamster ovary cells. The induction by LTD4 of monocyte chemoattractant protein-1 and interleukin-8 mRNAs in human monocytic leukemia THP-1 cells expressing CysLT1R was dose-dependently suppressed not only by mAbLTC but also by scFvLTC. LTC4- and LTD4-induced aggregation of mouse platelets expressing CysLT2R was dose-dependently suppressed by either mAbLTC or scFvLTC. Administration of mAbLTC reduced pulmonary eosinophil infiltration and goblet cell hyperplasia observed in a murine model of asthma. Furthermore, mAbLTC bound to CysLT2R antagonists but not to CysLT1R antagonists.Conclusions
These results indicate that mAbLTC and scFvLTC neutralize the biological activities of LTs by competing their binding to CysLT1R and CysLT2R. Furthermore, the binding of cysteinyl LT receptor antagonists to mAbLTC suggests the structural resemblance of the LT-recognition site of the antibody to that of these receptors.General significance
mAbLTC can be used in the treatment of inflammatory diseases such as asthma. 相似文献242.
Yamashita T Kamata M Endo S Yamamoto M Kakegawa K Watanabe H Miwa K Yamano T Funata M Sakamoto J Tani A Mol CD Zou H Dougan DR Sang B Snell G Fukatsu K 《Bioorganic & medicinal chemistry letters》2011,21(21):6314-6318
The co-crystal structure of the human acetyl-coenzyme A 2 (ACC2) carboxyl transferase domain and the reported compound CP-640186 (1b) suggested that two carbonyl groups are essential for potent ACC2 inhibition. By focusing on enhancing the interactions between the two carbonyl groups and the amino acid residues Gly(2162) and Glu(2230), we used ligand- and structure-based drug design to discover spirolactones bearing a 2-ureidobenzothiophene moiety. 相似文献
243.
In this study, a new method is proposed to estimate the torque-vector directions of each shoulder muscle. The method is based on a multiple regression model that reconstructs shoulder torque, which is calculated from the hand force and posture, from the surface EMG of many muscles recorded simultaneously. The torque-vector directions of eleven shoulder muscles of four subjects were obtained at up to 30 different arm postures with this method. The mean confidence interval (p < 0.05) of the estimated torque-vector direction of each subject was 7.7-10.6 degrees. The correlation coefficient between the measured shoulder torque and reconstructed shoulder torque was between 0.76-0.84. The results for majority of the muscles were in accordance with previous studies, and reasonable from the viewpoint of anatomy. The torque-vector directions of a muscle, which are estimated with this method, have more of a functional meaning than a pure anatomical or mechanical one. These indicate the direction of the shoulder torque accompanying the muscle activation for a normal shoulder action that involves the cooperative contraction of many muscles. 相似文献
244.
245.
A kidney injury molecule‐1 (Kim‐1) gene reporter in a mouse artificial chromosome: the responsiveness to cisplatin toxicity in immortalized mouse kidney S3 cells 下载免费PDF全文
246.
Asaumi H Watanabe S Taguchi M Tashiro M Otsuki M 《American journal of physiology. Gastrointestinal and liver physiology》2007,293(5):G972-G978
Local tissue pressure is higher in chronic pancreatitis than in the normal pancreas. We reported recently that pressure application induces synthesis of extracellular matrix (ECM) and cytokines in pancreatic stellate cells (PSCs) and that epigallocatechin gallate (EGCG), a potent antioxidant, inhibits the transformation of PSCs from quiescent to activated phenotype and ethanol-induced synthesis of ECM and cytokines in PSCs. These results suggest that oxidative stress and reactive oxygen species (ROS) are important in PSC activation. The aim of this study was to clarify the effects of ROS on activation and functions of pressure-stimulated PSCs. We used freshly isolated rat PSCs and culture-activated PSCs. Pressure was applied on rat cultured PSCs by adding compressed helium gas into a pressure-loading apparatus. PSCs were cultured with or without antioxidants (EGCG and N-acetyl cysteine) under normal or elevated pressure. Externally applied high pressure (80 mmHg) resulted in a gradual decrease of superoxide dismutase activity in PSCs and increased intracellular ROS generation as early as 30 s, reaching a peak level at 1 h. Antioxidants significantly inhibited ROS generation. Pressure increased the expression levels of alpha-smooth muscle actin, alpha(1)(I)-procollagen, and TGF-beta1 in PSCs. EGCG suppressed these alterations, abolished pressure-induced phosphorylation of p38 MAPK, and suppressed pressure-induced PSC transformation to activated phenotype. Our results indicated that ROS is a key player in pressure-induced PSC activation and ECM synthesis. Antioxidants could be potentially effective against the development of pancreatic fibrosis in patients with chronic pancreatitis. 相似文献
247.
248.
Noboru Ōtake Haruo Seto Mitsuo Koenuma 《Bioscience, biotechnology, and biochemistry》2013,77(10):1879-1886
The complete 18C-NMR assignment of lysocellin sodium salt has been obtained based on the 13C-13C double labeling method and comparison with its retroaldol degradation product as well as a structurally related polyether antibiotic, lasalocid A.In parallel, the biosynthesis of lysocellin was investigated by feeding 13C-labeled precursors followed by analyzing the resulting labeling patterns of the 13C-NMR spectra; a pathway to the antibiotic molecule is suggested which proceeds through condensation of two butyrate, eight propionate and one acetate units.In addition, a conversion of butyrate to propionate during the metabolic process has been disclosed. 相似文献
249.
Kenji Maekaji Mitsuo Sunagawa Hiroshi Imai 《Bioscience, biotechnology, and biochemistry》2013,77(3):165-169
Two kinds of anthocyanin were isolated from the petals of white peach and examined by paper chromatographic and spectral analyses. The results showed that one of them is crysanthemin and the other is a derivative of chrysanthemin which has not been isolated from peaches previously. 相似文献
250.
JH Choi K Maeda H Hirai E Harada M Kawade J Qi M Ojika H Kawagishi 《Bioscience, biotechnology, and biochemistry》2012,76(7):1407-1409
The novel cerebroside, termitomycesphin I (1), and two known cerebrosides (2 and 3) were isolated from the edible mushroom, Termitomyces titanicus. The structures of 1-3 were determined and identified by interpreting the spectroscopic data. 相似文献