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101.
K Hashizume T Miyamoto K Ichikawa K Yamauchi A Sakurai H Ohtsuka M Kobayashi Y Nishii T Yamada 《The Journal of biological chemistry》1989,264(9):4864-4871
Cytosolic NADPH-dependent 3,5,3'-triiodo-L-thyronine (T3)-binding protein (CTBP) purified from rat kidney was further characterized in its T3 binding and its interaction with nuclei. Pretreatment of the CTBP with NADP induced dithiothreitol (DTT)-dependent T3 binding. The DTT-dependent T3 binding was increased by NADP in a concentration-dependent manner, and the maximal binding was obtained by 0.1 microM NADP. Higher concentrations of NADP (more than 0.1 microM), however, reduced T3 binding. NAD also induced DTT-dependent T3 binding, but was very low compared to that induced by NADP. NADPH and NADH did not produce DTT-dependent T3 binding. This NADP-activated, DTT-dependent T3 binding was characterized as follows: Ka for T3 binding was 1.8 x 10(9) M-1, and the maximal binding capacity was 15,000 pmol/mg of protein in the CTBP activated by 0.1 microM NADP. The molecular weight of the CTBP was 58,000 (4.7 S). A complex of [125I]T3 and CTBP (NADP.DTT.CTBP.[125I]T3), which was made from the CTBP pretreated with NADP and DTT, did not bind to DNA. However, the complex bound to the nuclei prepared from rat kidney. Treatment of the nuclei with 0.38 M KCl and with DNase I did not lead to loss of the binding activity for the complex. Treatment of nuclei with 0.5 M NaCl led to the loss of the activity for binding the complex. A complex of [125I]T3 and NADPH-activated CTBP did not bind these nuclear preparations. These results suggested that the active form of CTBP is present in two different forms: one is NADPH-activated, which plays a role as a reservoir for cytoplasmic T3, and the other is NADP-activated, which plays a role as a T3 carrier protein that transfers T3 from cytoplasm to nucleus. 相似文献
102.
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104.
Hashizume C Kuramitsu M Zhang X Kurosawa T Kamata M Aida Y 《Microbes and infection / Institut Pasteur》2007,9(4):490-497
Vpr, an accessory gene product of human immunodeficiency virus type 1 (HIV-1), affects both viral and cellular proliferation by mediating long terminal repeat activation, cell cycle arrest at the G2 phase, and apoptosis. We previously found that Vpr plays a novel role as a regulator of pre-mRNA splicing both in vivo and in vitro. However, the cellular target of Vpr, as well as the mechanism of cellular pre-mRNA splicing inhibition by Vpr, is unknown. Here, we show clearly that Vpr inhibits the splicing of cellular pre-mRNA, such as beta-globin pre-mRNA and immunoglobulin (Ig) M pre-mRNA and that the third alpha-helical domain and arginine-rich region are important its ability to inhibit splicing. Additionally, using mutants with specific substitutions in two domains of Vpr, we demonstrated that the interaction between Vpr and SAP145, an essential splicing factor, was indispensable for splicing inhibition. Finally, co-immunoprecipitation and in vitro competitive binding assays indicated that Vpr associates with SAP145 and interferes with SAP145-SAP49 complex formation. Thus, these results suggest that cellular expression of Vpr may block spliceosome assembly by interfering with the function of the SAP145-SAP49 complex in host cells. 相似文献
105.
Hashizume S Iwanuma S Akagi R Kanehisa H Kawakami Y Yanai T 《Journal of biomechanics》2012,45(2):409-413
Two-dimensional methods have been applied to determine the Achilles tendon moment arm in previous studies, although the talocrural joint rotates in three-dimension. The purpose of this study was to develop a method for determining the Achilles tendon moment arm in three-dimensions (3DMA). A series of sagittal ankle images were obtained at ankle positions of -20°, -10° (dorsiflexed position), 0° (neutral position), +10°, +20°, and +30° (plantarflexed position). The talocrural joint axis was determined as the finite helical axis of the ankle joint over 20° of displacement, and the 3DMA was determined as the shortest distance from the talocrural joint axis to the line of action of the Achilles tendon force. The corresponding 2DMA was determined with the center of rotation method using the images captured on the sagittal plane passing through the mid-point of the medio-lateral width of the tibia. The 3DMA ranged from 35 to 41 mm across various ankle positions and was, on average, 11 mm smaller than 2DMA. The difference between the two measures was attributable primarily to the deviations of the talocrural joint axis from the anatomical medio-lateral direction. The deviations on the coronal plane (21.4±20.7°) and on the transverse planes (14.8±22.6°) accounted for the errors of 1.3 mm and 3.0 mm, respectively. In addition, selecting either a medially or laterally misaligned sagittal-plane image for determining the 2DMA gave rise to error by 3.5 mm. The remaining difference was accounted for by the random measurement error. 相似文献
106.
Odan M Ishizuka N Hiramatsu Y Inagaki M Hashizume H Fujii Y Mitsumori S Morioka Y Soga M Deguchi M Yasui K Arimura A 《Bioorganic & medicinal chemistry letters》2012,22(8):2894-2897
Our lead compound 1 showed high affinity for both CB1 and CB2 receptors, suggesting the possibility of inducing psychoactive side effects through the CB1 receptor in the brain. To solve this issue, polar functional groups were introduced at the 3-position of the pyridone core of compound 1 to find CB1/2 dual agonists such as 17 and 20 which did not show any CNS side effects. 相似文献
107.
K Takeda T Terauchi M Hashizume K Shin M Ino H Shibata M Yonaga 《Bioorganic & medicinal chemistry letters》2012,22(17):5372-5378
We designed and synthesized a series of 2-Ar-8-methyl-5-alkylaminolquinolines as potent corticotropin-releasing factor 1 (CRF(1)) receptor antagonists. The structure-activity relationships of substituents at each position (R(3), R(5), R(5'), and R(8)) was investigated. By derivatization, three compounds (6, 14b, and 14c) were identified as orally active CRF(1) receptor antagonists. 相似文献
108.
K Hashizume T Ito M Shimohashi A Kokita T Tokiwano M Okuda 《Bioscience, biotechnology, and biochemistry》2012,76(7):1291-1295
The taste-active hydrophobic compounds in a charcoal-untreated sake sample were subjected to a taste dilution analysis (TDA). All of the high-TDA factor fractions showed a bitter or astringent taste in common, but their taste characters were different. The taste-active compounds of the high-TDA factor fractions were purified by taste-guided fractionation, using RP-HPLC and an instrumental analysis. From each of the seven fractions, ferulic acid, ethyl ferulate, tryptophol, three previously reported bitter-tasting peptides, and two novel ethyl esters of the peptides of 10 amino acid residues were identified. All the identified compounds had a similar taste character to that of the TDA fractions analyzed. Ethyl ferulate and the ethyl ester of the peptides showed a moderately bitter taste. The concentration of the identified compounds in seven jyunmai-type sake samples was determined. This concentration was decreased dose dependently by a charcoal treatment which is commonly applied in the final step of sake manufacture, notably with the compounds of high hydrophobicity. 相似文献
109.
110.
We have characterized cytochromes P450, CYP710A13, and CYP710A14, as the sterol C22-desaturase in the moss Physcomitrella patens. GC–MS analyses demonstrated that P. patens accumulated stigmasterol as the major sterol (56–60% of total sterol) and sitosterol to a lesser extent (8–12%); this sterol
profile contrasts with those in higher plants accumulating stigmasterol as a minor component. Recombinant CYP710A13 and CYP710A14
proteins prepared using a baculovirus/insect cell system exhibited the C22-desaturase activity with β-sitosterol to produce
stigmasterol, while campesterol and 24-epi-campesterol were not accepted as the substrates. The K
m values for β-sitosterol of CYP710A13 (1.0 ± 0.043 μM) and CYP710A14 (2.1 ± 0.17 μM) were at comparable levels of those reported
with higher plant CYP710A proteins. In Arabidopsis T87 cells over-expressing CYP710A14, stigmasterol contents reached a level 20- to 72-fold higher than those in the basal
level of T87 cells, confirming the C22-desaturase activity of this P450 enzyme. The occurrence of the end-products together
with the enzymes involved in the last step of the pathway substantiated the presence of an entire sterol biosynthetic pathway
in P. patens, providing evidence for the conservation of the sterol biosynthetic pathway through the evolutionary process of land plants.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users. 相似文献