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951.
Ohi A Hanabusa E Ueda O Segawa H Horiba N Kaneko I Kuwahara S Mukai T Sasaki S Tominaga R Furutani J Aranami F Ohtomo S Oikawa Y Kawase Y Wada NA Tachibe T Kakefuda M Tateishi H Matsumoto K Tatsumi S Kido S Fukushima N Jishage K Miyamoto K 《American journal of physiology. Renal physiology》2011,301(5):F1105-F1113
An inorganic phosphate (P(i))-restricted diet is important for patients with chronic kidney disease and patients on hemodialysis. Phosphate binders are essential for preventing hyperphosphatemia and ectopic calcification. The sodium-dependent P(i) (Na/P(i)) transport system is involved in intestinal P(i) absorption and is regulated by several factors. The type II sodium-dependent P(i) transporter Npt2b is expressed in the brush-border membrane in intestinal epithelial cells and transports P(i). In the present study, we analyzed the phenotype of Npt2b(-/-) and hetero(+/-) mice. Npt2b(-/-) mice died in utero soon after implantation, indicating that Npt2b is essential for early embryonic development. At 4 wk of age, Npt2b(+/-) mice showed hypophosphatemia and low urinary P(i) excretion. Plasma fibroblast growth factor 23 levels were significantly decreased and 1,25(OH)(2)D(3) levels were significantly increased in Npt2b(+/-) mice compared with Npt2b(+/+) mice. Npt2b mRNA levels were reduced to 50% that in Npt2b(+/+) mice. In contrast, renal Npt2a and Npt2c transporter protein levels were significantly increased in Npt2b(+/-) mice. At 20 wk of age, Npt2b(+/-) mice showed hypophosphaturia and reduced Na/P(i) cotransport activity in the distal intestine. Npt2b(+/+) mice with adenine-induced renal failure had hyperphosphatemia and high plasma creatinine levels. Npt2b(+/-) mice treated with adenine had significantly reduced plasma P(i) levels compared with Npt2b(+/+) mice. Intestinal Npt2b protein and Na(+)/P(i) transport activity levels were significantly lower in Npt2b(+/-) mice than in the Npt2b(+/+) mice. The findings of the present studies suggest that Npt2b is an important target for the prevention of hyperphosphatemia. 相似文献
952.
The RUN domain is a less conserved protein motif that consists of approximately 70 amino acids, and because RUN domains are often found in proteins involved in the regulation of Rab small GTPases, the RUN domain has been suggested to be involved in Rab-mediated membrane trafficking, possibly as a Rab-binding site. However, since the Rab binding activity of most RUN domains has never been investigated, in this study we performed a genome-wide analysis of the Rab binding activity of the RUN domains of 19 different RUN domain-containing proteins by yeast two-hybrid assays with 60 different Rabs as bait. The results showed that only six of them interact with specific Rab isoforms with different Rab binding specificity, i.e., DENND5A/B with Rab6A/B, PLEKHM2 with Rab1A, RUFY2/3 with Rab33, and RUSC2 with Rab1/Rab35/Rab41. We also identified the minimal functional Rab35-binding site of RUSC2 (amino acid residues 982-1199) and succeeded in developing a novel GTP-Rab35-specific trapper, which we named RBD35 (Rab-binding domain specific for Rab35). Recombinant RBD35 was found to trap GTP-Rab35 specifically both in vitro and in PC12 cells, and overexpression of fluorescently tagged RBD35 in PC12 cells strongly inhibited nerve growth factor-dependent neurite outgrowth. 相似文献
953.
954.
Yamashita S Fukushima H Akiyama Y Niidome Y Mori T Katayama Y Niidome T 《Bioorganic & medicinal chemistry》2011,19(7):2130-2135
Gold nanorods have strong absorption bands in the near-infrared region, in which light penetrates deeply into tissues. The absorbed light energy is converted into heat by gold nanorods, the so-called 'photothermal effect'. Hence, gold nanorods are expected to act not only as on-demand thermal converters for photothermal therapy but also as controllers of a drug-release system responding to irradiation by near-infrared light. To achieve a controlled-release system that can be triggered by light irradiation, double-stranded DNA (dsDNA) was modified on gold nanorods. When the dsDNA-modified gold nanorods were irradiated by near-infrared light, the single-stranded DNA (ssDNA) was released from gold nanorods due to the photothermal effect. The amount of released ssDNA was dependent upon the power and exposure time of light irradiation. Release of ssDNA was also observed in tumors grown on mice after light irradiation. Such a controlled-release system of oligonucleotide triggered by the photothermal effect could expand the applications of gold nanorods that have unique optical characteristics in medicinal fields. 相似文献
955.
Seki H Sawai S Ohyama K Mizutani M Ohnishi T Sudo H Fukushima EO Akashi T Aoki T Saito K Muranaka T 《The Plant cell》2011,23(11):4112-4123
Glycyrrhizin, a triterpenoid saponin derived from the underground parts of Glycyrrhiza plants (licorice), has several pharmacological activities and is also used worldwide as a natural sweetener. The biosynthesis of glycyrrhizin involves the initial cyclization of 2,3-oxidosqualene to the triterpene skeleton β-amyrin, followed by a series of oxidative reactions at positions C-11 and C-30, and glycosyl transfers to the C-3 hydroxyl group. We previously reported the identification of a cytochrome P450 monooxygenase (P450) gene encoding β-amyrin 11-oxidase (CYP88D6) as the initial P450 gene in glycyrrhizin biosynthesis. In this study, a second relevant P450 (CYP72A154) was identified and shown to be responsible for C-30 oxidation in the glycyrrhizin pathway. CYP72A154 expressed in an engineered yeast strain that endogenously produces 11-oxo-β-amyrin (a possible biosynthetic intermediate between β-amyrin and glycyrrhizin) catalyzed three sequential oxidation steps at C-30 of 11-oxo-β-amyrin supplied in situ to produce glycyrrhetinic acid, a glycyrrhizin aglycone. Furthermore, CYP72A63 of Medicago truncatula, which has high sequence similarity to CYP72A154, was able to catalyze C-30 oxidation of β-amyrin. These results reveal a function of CYP72A subfamily proteins as triterpene-oxidizing enzymes and provide a genetic tool for engineering the production of glycyrrhizin. 相似文献
956.
Yoshito Nagano Toru Fukushima Kazuo Okemoto Keiichiro Tanaka David DL Bowtell Ze'ev A Ronai John C Reed Shu-ichi Matsuzawa 《Cell cycle (Georgetown, Tex.)》2011,10(15):2592-2602
p27kip1 has been implicated in cell cycle regulation, functioning as an inhibitor of cyclin-dependent kinase activity. In addition, p27 was also shown to affect cell migration, with accumulation of cytoplasmic p27 associated with tumor invasiveness. However, the mechanism underlying p27 regulation as a cytoplasmic protein is poorly understood. Here we show that glucose starvation induces proteasome-dependent degradation of cytoplasmic p27, accompanied by a decrease in cell motility. We also show that the glucose limitation-induced p27 degradation is regulated through an ubiquitin E3 ligase complex involving Siah1 and SIP/CacyBP. SIP−/− embryonic fibroblasts have increased levels of cytosolic p27 and exhibit increased cell motility compared with wild-type cells. These observations suggest that the Siah1/SIP E3 ligase complex regulates cell motility through degradation of p27.Key words: p27kip1, Siah1, SIP, glucose starvation, cell migration 相似文献
957.
Qian Fu Naoya Fukushima Haruo Maeda Kozo Sato 《Bioscience, biotechnology, and biochemistry》2013,77(7):1200-1206
We examined whether a hyperthermophilic microbial fuel cell (MFC) would be technically feasible. Two-chamber MFC reactors were inoculated with subsurface microorganisms indigenous to formation water from a petroleum reservoir and were started up at operating temperature 80 °C. The MFC generated a maximum current of 1.3 mA 45 h after the inoculation. Performance of the MFC improved with an increase in the operating temperature; the best performance was achieved at 95 °C with the maximum power density of 165 mWm?2, which was approximately fourfold higher than that at 75 °C. Thus, to our knowledge, our study is the first to demonstrate generation of electricity in a hyperthermophilic MFC (operating temperature as high as 95 °C). Scanning electron microscopy showed that filamentous microbial cells were attached on the anode surface. The anodic microbial consortium showed limited phylogenetic diversity and primarily consisted of hyperthermophilic bacteria closely related to Caldanaerobacter subterraneus and Thermodesulfobacterium commune. 相似文献
958.
Kazuya Hayashi Danji Fukushima Koya Mogi 《Bioscience, biotechnology, and biochemistry》2013,77(10):1237-1241
The alkaline proteinase of Aspergillus sojae was isolated in gram quantities as a homogeneous form. The purification procedures were, (1) batchwise-treatment with ion exchange resin Duolite CS 101, (2) fractional precipitation with ammonium sulfate, (3) precipitation with acetone, (4) column chromatography on DEAE-cellulose, and (5) gel filtration with Sephadex G-100. The recovery of the activity was about 12%. The purified enzyme preparation was found to be homogeneous by several criteria such as ultracentrifugation, paper and moving-boundary electrophoreses, etc. Any kinds of carbohydrate and phosphorus were not detected in this preparation, suggesting that this enzyme is a simple protein. 相似文献
959.
Yukiko Hiraiwa Akihiro Morinaka Takayoshi Fukushima Toshiaki Kudo 《Bioorganic & medicinal chemistry》2013,21(18):5841-5850
3-Alkyloxy and 3-amino phthalic acid derivatives were found to have metallo-β-lactamase inhibitory activity. Among them, 3-amino phthalic acid derivatives showed both potent activity against metallo-β-lactamase, IMP-1 inhibitory activity and a strong combination effect with biapenem (BIPM), carbapenem antibiotic. In particular, the 4′-hydroxy-piperidine derivative showed strong IMP-1 inhibitory activity and a combination effect with various antibiotics. 相似文献
960.
Mai Fukushima Kazuhiro Iiyama Jun Yamashita Masutaka Furue Gaku Tsuji Shigeo Imanishi 《Preparative biochemistry & biotechnology》2013,43(6):565-576
The recombinant proteins with strong antimicrobial activity are known to be very difficult to express using bacterial expression system. Here, human β-defensin (DEFB) 1, DEFB2, and DEFB3 were successfully produced using a silkworm–baculovirus protein expression system. We have generated four baculoviruses for each DEFB protein to compare the effect of different peptide tags in secretion into silkworm larval hemolymph. Interestingly, the best performing peptide tags for the secretion were different among DEFBs: C-terminal GST-H8 tag for DEFB1, N-terminal H8 tag for DEFB2, and C-terminal H8 tag for DEFB3, respectively. In addition, the colony count assay demonstrated that the recombinant DEFB2 s showed antimicrobial activities against Escherichia coli, Pseudomonas aeruginosa, and Paenibacillus thiaminolyticus. 相似文献