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91.
Lin H Sugimoto Y Ohsaki Y Ninomiya H Oka A Taniguchi M Ida H Eto Y Ogawa S Matsuzaki Y Sawa M Inoue T Higaki K Nanba E Ohno K Suzuki Y 《Biochimica et biophysica acta》2004,1689(3):219-228
Gaucher disease (GD) is the most common form of sphingolipidosis and is caused by a defect of beta-glucosidase (beta-Glu). A carbohydrate mimic N-octyl-beta-valienamine (NOV) is an inhibitor of beta-Glu. When applied to cultured GD fibroblasts with F213I beta-Glu mutation, NOV increased the protein level of the mutant enzyme and up-regulated cellular enzyme activity. The maximum effect of NOV was observed in F213I homozygous cells in which NOV treatment at 30 microM for 4 days caused a approximately 6-fold increase in the enzyme activity, up to approximately 80% of the activity in control cells. NOV was not effective in cells with other beta-Glu mutations, N370S, L444P, 84CG and RecNciI. Immunofluorescence and cell fractionation showed localization of the F213I mutant enzyme in the lysosomes of NOV-treated cells. Consistent with this, NOV restored clearance of 14C-labeled glucosylceramide in F213I homozygous cells. F213I mutant beta-Glu rapidly lost its activity at neutral pH in vitro and this pH-dependent loss of activity was attenuated by NOV. These results suggest that NOV works as a chemical chaperone to accelerate transport and maturation of F213I mutant beta-Glu and may suggest a therapeutic value of this compound for GD. 相似文献
92.
Overexpression of CNP in chondrocytes rescues achondroplasia through a MAPK-dependent pathway 总被引:17,自引:0,他引:17
Yasoda A Komatsu Y Chusho H Miyazawa T Ozasa A Miura M Kurihara T Rogi T Tanaka S Suda M Tamura N Ogawa Y Nakao K 《Nature medicine》2004,10(1):80-86
Achondroplasia is the most common genetic form of human dwarfism, for which there is presently no effective therapy. C-type natriuretic peptide (CNP) is a newly identified molecule that regulates endochondral bone growth through GC-B, a subtype of particulate guanylyl cyclase. Here we show that targeted overexpression of CNP in chondrocytes counteracts dwarfism in a mouse model of achondroplasia with activated fibroblast growth factor receptor 3 (FGFR-3) in the cartilage. CNP prevented the shortening of achondroplastic bones by correcting the decreased extracellular matrix synthesis in the growth plate through inhibition of the MAPK pathway of FGF signaling. CNP had no effect on the STAT-1 pathway of FGF signaling that mediates the decreased proliferation and the delayed differentiation of achondroplastic chondrocytes. These results demonstrate that activation of the CNP-GC-B system in endochondral bone formation constitutes a new therapeutic strategy for human achondroplasia. 相似文献
93.
Nguyen Van Tho Le Thi Huyen Trang Yoshitaka Murakami Emiko Ogawa Yasushi Ryujin Rie Kanda Hiroaki Nakagawa Kenichi Goto Kentaro Fukunaga Yuichi Higami Ruriko Seto Taishi Nagao Tetsuya Oguma Masafumi Yamaguchi Le Thi Tuyet Lan Yasutaka Nakano 《PloS one》2014,9(5)
Background
It is time-consuming to obtain the square root of airway wall area of the hypothetical airway with an internal perimeter of 10 mm (√Aaw at Pi10), a comparable index of airway dimensions in chronic obstructive pulmonary disease (COPD), from all airways of the whole lungs using 3-dimensional computed tomography (CT) analysis. We hypothesized that √Aaw at Pi10 differs among the five lung lobes and √Aaw at Pi10 derived from one certain lung lobe has a high level of agreement with that derived from the whole lungs in smokers.Methods
Pulmonary function tests and chest volumetric CTs were performed in 157 male smokers (102 COPD, 55 non-COPD). All visible bronchial segments from the 3rd to 5th generations were segmented and measured using commercially available 3-dimensional CT analysis software. √Aaw at Pi10 of each lung lobe was estimated from all measurable bronchial segments of that lobe.Results
Using a mixed-effects model, √Aaw at Pi10 differed significantly among the five lung lobes (R2 = 0.78, P<0.0001). The Bland-Altman plots show that √Aaw at Pi10 derived from the right or left upper lobe had a high level of agreement with that derived from the whole lungs, while √Aaw at Pi10 derived from the right or left lower lobe did not.Conclusion
In male smokers, CT-derived airway wall area differs among the five lung lobes, and airway wall area derived from the right or left upper lobe is representative of the whole lungs. 相似文献94.
Shizuya Kabuto Tomohisa Ogawa Koji Muramoto Vaughan Oosthuizen Ryno J. Naude 《Comparative biochemistry and physiology. Part B, Biochemistry & molecular biology》2000,127(4)
The amino-acid sequence of α-amylase isolated from the pancreas of the ostrich, Struthio camelus was determined. The α-amylase (OPA) consisted of 497 amino acid residues with pyroglutamic acid at the N-terminus and no oligosaccharide. Amino acid identity between OPA and chicken, porcine and human pancreatic α-amylases individually, was found to be 88, 82 and 86%, respectively. 相似文献
95.
96.
Huiling Dai Lili Zhang Jingsong Zhang Hualing Mi Teruo Ogawa Weimin Ma 《The Plant journal : for cell and molecular biology》2013,75(5):858-866
Despite significant progress in clarifying the subunit compositions and functions of the multiple NADPH dehydrogenase (NDH‐1) complexes in cyanobacteria, the subunit maturation and assembly of their NDH‐1 complexes are poorly understood. By transformation of wild‐type cells with a transposon‐tagged library, we isolated three mutants of Synechocystis sp. PCC 6803 defective in NDH‐1‐mediated cyclic electron transfer and unable to grow under high light conditions. All the mutants were tagged in the same slr1097 gene, encoding an unknown protein that shares significant homology with the Arabidopsis protein chlororespiratory reduction 6 (CRR6). The slr1097 product was localized in the cytoplasm and was required for efficient assembly of NDH‐1 complexes. Analysis of the interaction of Slr1097 with 18 subunits of NDH‐1 complexes using a yeast two‐hybrid system indicated a strong interaction with NdhI but not with other Ndh subunits. Absence of Slr1097 resulted in a significant decrease of NdhI in the cytoplasm, but not of other Ndh subunits including NdhH, NdhK and NdhM; the decrease was more evident in the cytoplasm than in the thylakoid membranes. In the ?slr1097 mutant, NdhH, NdhI, NdhK and NdhM were hardly detectable in the NDH‐1M complex, whereas almost half the wild‐type levels of these subunits were present in NDH‐1L complex; similar results were observed in the NdhI‐less mutant. These results suggest that Slr1097 is involved in the maturation of NdhI, and that assembly of the NDH‐1M complex is strongly dependent on this factor. Maturation of NdhI appears not to be crucial to assembly of the NDH‐1L complex. 相似文献
97.
K Ogawa M Tashima Y Yumoto T Okuda H Sawada M Okuma Y Maruyama 《Nucleic acids research》1990,18(23):7169
98.
The saccharification of agricultural woody wastes was studied using a commercial enzyme preparation, Cellulase onozuka, derived from Trichoderma viride or the solid culture extracts of the fungus. With the intention of producing sugar at low cost, a simple procedure of enzymatic saccharification of rice straw, bagasse, and sawdust was studied. Delignifying methods of these wastes were investigated using dilute sodium hydroxide solution and dilute peracetic acid. Rice straw and bagasse were effectively delignified by boiling in a 1% sodium hydroxide solution for 3 hr or by autoclaving at 120 degrees C in a 1% sodium hydroxide solution for 1 hr. The sawdust from a broad leaved tree (Machilus thunbergii) was delignified by autoclaving at 120 degrees C in a 1% sodium hydroxide solution for 1 hr and by subsequent boiling in diluted 1/5 peracetic acid for 1 hr. This type of sawdust was also delignified by boiling in 1/5 peracetic acid for 1 hr and by subsequent autoclaving at 120 degrees C in a 1% sodium hydroxide solution for 1 hr. The sawdust from a coniferous tree (Cryptomeria japonica) was delignified by boiling in 1/5 peracetic acid for 1 hr and by subsequent autoclaving at 120 degrees C in a 1% sodium hydroxide solution for 1 hr; however, the successive treatment by autoclaving with alkali solution and subsequent boiling with diluted peracetic acid failed to bring about the desired effect. The saccharification of delignified rice straw, bagasse, and sawdust was examined using Cellulase onozuka, wheat bran or rice straw solid culture at various substrate concentrations, resulting in the formation of 5 to 10% sugar solutions after incubation at pH 5.0, 45 degrees C for 48 hr. The optimum substrate concentration existed at around 10%. Reuse of cellulase solution and resaccharification of residual sawdust were considered to be inadequate. 相似文献
99.
Chikara Komiya Kyoichiro Tsuchiya Kumiko Shiba Yasutaka Miyachi Shunsaku Furuke Noriko Shimazu Shinobu Yamaguchi Kazuo Kanno Yoshihiro Ogawa 《PloS one》2016,11(3)
Type 2 diabetes mellitus (T2DM) is associated with a high incidence of non-alcoholic fatty liver disease (NAFLD) related to obesity and insulin resistance. Currently, medical interventions for NAFLD have focused on diet control and exercise to reduce body weight, and there is a requirement for effective pharmacological therapies. Sodium-glucose cotransporter 2 (SGLT2) inhibitors are oral antidiabetic drugs that promote the urinary excretion of glucose by blocking its reabsorption in renal proximal tubules. SGLT2 inhibitors lower blood glucose independent of insulin action and are expected to reduce body weight because of urinary calorie loss. Here we show that an SGLT2 inhibitor ipragliflozin improves hepatic steatosis in high-fat diet-induced and leptin-deficient (ob/ob) obese mice irrespective of body weight reduction. In the obese mice, ipragliflozin-induced hyperphagia occurred to increase energy intake, attenuating body weight reduction with increased epididymal fat mass. There is an inverse correlation between weights of liver and epididymal fat in ipragliflozin-treated obese mice, suggesting that ipragliflozin treatment promotes normotopic fat accumulation in the epididymal fat and prevents ectopic fat accumulation in the liver. Despite increased adiposity, ipragliflozin ameliorates obesity-associated inflammation and insulin resistance in epididymal fat. Clinically, ipragliflozin improves liver dysfunction in patients with T2DM irrespective of body weight reduction. These findings provide new insight into the effects of SGLT2 inhibitors on energy homeostasis and fat accumulation and indicate their potential therapeutic efficacy in T2DM-associated hepatic steatosis. 相似文献
100.
Ashida H Ogawa M Kim M Suzuki S Sanada T Punginelli C Mimuro H Sasakawa C 《Current opinion in microbiology》2011,14(1):16-23
Although the intestinal epithelium is equipped with multiple defense systems that sense bacterial components, transmit alarms to the immune system, clear the bacteria, and renew the injured epithelial lining, mucosal bacterial pathogens are capable of efficiently colonizing the intestinal epithelium, because they have evolved systems that modulate the inflammatory and immune responses of the host and exploit the harmful environments as replicative niches. In this review we highlight current topics concerning Shigella's tactics that interfere with the innate immune systems. 相似文献