排序方式: 共有100条查询结果,搜索用时 15 毫秒
31.
Minehira D Takeda D Urata H Kato A Adachi I Wang X Matsuya Y Sugimoto K Takemura M Endo S Matsunaga T Hara A Koseki J Narukawa K Hirono S Toyooka N 《Bioorganic & medicinal chemistry》2012,20(1):356-367
New substituted (1-thioxo-1,2,3,4-tetrahydro-β-carbolin-9-yl)acetic acids were designed as the inhibitor of AKR1B1 based upon the structure of rhetsinine, a minor alkaloidal component of Evodia rutaecarpa, and twenty derivatives were synthesized and evaluated. The most active compound of the series was (2-benzyl-6-methoxy-1-thioxo-1,2,3,4-tetrahydro-β-carbolin-9-yl)acetic acid (7m), which showed comparable inhibitory activity for AKR1B1 (IC(50)=0.15μM) with clinically used epalrestat (IC(50)=0.1μM). In the view of activity and selectivity, the most potent compound was (2-benzyl-6-carboxy-1-thioxo-1,2,3,4-tetrahydro-β-carbolin-9-yl)acetic acid (7t), which showed strong inhibitory effect (IC(50)=0.17μM) and very high selectivity for AKR1B1 against AKR1A1 (311:1) and AKR1B10 (253:1) compared with epalrestat. 相似文献
32.
Hayashi K Lee JB Maitani Y Toyooka N Nemoto H Hayashi T 《The journal of gene medicine》2006,8(8):1056-1067
BACKGROUND: The most extensively investigated strategy of suicide gene therapy for treatment of cancer is the transfer of the herpes simplex virus thymidine kinase (HSV-TK) gene followed by administration of antiviral prodrugs such as acyclovir (ACV) and ganciclovir (GCV). The choice of the agent that can stimulate HSV-TK enzymatic activity is one of the determinants of the usefulness of this strategy. Previously, we found that a diterpenoid, scopadulciol (SDC), produced a significant increase in the active metabolite of ACV. This suggests that SDC may play a role in the HSV-TK/prodrug administration system. METHODS: The anticancer effect of SDC was evaluated in HSV-TK-expressing (TK+) cancer cells and nude mice bearing TK+ tumors. In vitro and in vivo enzyme assays were performed using TK+ cells and tumors. The phosphorylation of ACV monophosphate (ACV-MP) was measured in TK- cell lysates. The pharmacokinetics of prodrugs was evaluated by calculating area-under-the-concentration-time-curve values. RESULTS: SDC stimulated HSV-TK activity in TK+ cells and tumors, and increased GCV-TP levels, while no effect of SDC was observed on the phosphorylation of ACV-MP to ACV-TP by cellular kinases. The SDC/prodrug combination altered the pharmacokinetics of the prodrugs. In accord with these findings, SDC enhanced significantly the cell-killing activity of prodrugs. The bystander effect was also significantly augmented by the combined treatment of ACV/GCV and SDC. CONCLUSIONS: SDC was shown to be effective in the HSV-TK/prodrug administration system and improved the efficiency of the bystander effect of ACV and GCV. The findings will be considerably valuable with respect to the use of GCV in lower doses and less toxic ACV. This novel strategy of drug combination could provide benefit to HSV-TK/prodrug gene therapy. 相似文献
33.
Ryo Nakabayashi Kei Hashimoto Tetsuya Mori Kiminori Toyooka Hiroshi Sudo Kazuki Saito 《Plant Biotechnology》2021,38(3):311
Spatial metabolomics uses imaging mass spectrometry (IMS) to localize metabolites within tissue section. Here, we performed matrix-assisted laser desorption/ionization-Fourier transform ion cyclotron resonance-IMS (MALDI-FTICR-IMS) to identify the localization of asparaptine A, a naturally occurring inhibitor of angiotensin-converting enzyme, in green spears of asparagus (Asparagus officinalis). Spatial metabolome data were acquired in an untargeted manner. Segmentation analysis using the data characterized tissue-type-dependent and independent distribution patterns in cross-sections of asparagus spears. Moreover, asparaptine A accumulated at high levels in developing lateral shoot tissues. Quantification of asparaptine A in lateral shoots using liquid chromatography-tandem mass spectrometry (LC-MS/MS) validated the IMS analysis. These results provide valuable information for understanding the function of asparaptine A in asparagus, and identify the lateral shoot as a potential region of interest for multiomics studies to examine gene-to-metabolite associations in the asparaptine A biosynthesis. 相似文献
34.
Anura Pushpakumara Rathnayake Hirofumi Kadono Satoru Toyooka Makoto Miwa 《Environmental and Experimental Botany》2008,64(3):314-321
This study presents a new technique to measure root elongation of Japanese red pine (Pinus densiflora Seibold & Zucc.) seedlings with very high sensitivity in the order of sub-nanometer by using a novel optical interference method called statistical interferometry. The principle of the statistical interferometry is based on the statistics of a speckle field, which is generated when a rough surface is illuminated by a laser light. The technique facilitates to obtain minute root elongation measurements in the order of sub-seconds. The root elongation behavior of Pinus densiflora seedlings infected with ectomycorrhizal fungi, Pisolithus sp. (Ps) and Cenococcum geophilum Fr. (Cg), was investigated in comparison with that of an uninfected control. In the experiments, two points on a root with the separation of 3 mm were illuminated by laser beams and the elongation was measured continuously by analyzing speckle patterns successively taken by a CCD camera. The root elongation rate (RER), measured as the length of root elongation per second per millimeter (mean ± S.D.) for Ps-infected, Cg-infected and uninfected seedlings were 10.85 ± 2.41, 5.54 ± 1.43, and 2.41 ± 1.01 nm s?1 mm?1, respectively. We found that the RERs of seedlings infected with ectomycorrhizal fungi were significantly higher than that of the uninfected seedlings, and the seedlings infected with Ps fungi showed the highest RER. We conducted another experiment to observe two-dimensional root growth, in which the growth measurements were obtained for 4 months. From this experiment, we observed that root growth of ectomycorrhizal fungi infected seedlings were higher than that of the uninfected seedlings. The evaluation of results from these two techniques proves that the proposed statistical interferometry is much faster and very sensitive technique, where the time required for growth monitoring is 107 times less than the other. We can conclude that, at the scale of either very short time or relatively long time, the symbiotic relationship between root and ectomycorrhiza has a positive effect steadily on the root elongation. 相似文献
35.
Masaaki Fujita Yumiko Toyooka Hideyuki Tamegai Tadashi Eguchi Katsumi Kakinuma 《Journal of Molecular Catalysis .B, Enzymatic》2000,9(4-6):149-155
The crucial role of Arg-94 in 3-isopropylmalate (IPM) dehydrogenase from Thermus thermophilus HB8 was elucidated by replacing the residue to lysine with site-directed mutagenesis. The kcat value of the R94K mutant enzyme for IPM was significantly reduced to 1/170 compared with that of native enzyme, whereas the Km for IPM was not much changed. It appeared that the major role of Arg-94 in exerting the enzymatic activity is not for the substrate recognition, but for the reaction catalysis, in such a way that Arg-94 facilitates stabilization of the transition-state in the decarboxylation step. 相似文献
36.
Junichi Soh Naoki Okumura William W. Lockwood Hiromasa Yamamoto Hisayuki Shigematsu Wei Zhang Raj Chari David S. Shames Ximing Tang Calum MacAulay Marileila Varella-Garcia T?nu Vooder Ignacio I. Wistuba Stephen Lam Rolf Brekken Shinichi Toyooka John D. Minna Wan L. Lam Adi F. Gazdar 《PloS one》2009,4(10)
37.
A Chloroplastic UDP-Glucose Pyrophosphorylase from Arabidopsis Is the Committed Enzyme for the First Step of Sulfolipid Biosynthesis 总被引:1,自引:0,他引:1
38.
Aya Kitajima Satoru Asatsuma Hisao Okada Yuki Hamada Kentaro Kaneko Yohei Nanjo Yasushi Kawagoe Kiminori Toyooka Ken Matsuoka Masaki Takeuchi Akihiko Nakano Toshiaki Mitsui 《The Plant cell》2009,21(9):2844-2858
The well-characterized secretory glycoprotein, rice (Oryza sativa) α-amylase isoform I-1 (AmyI-1), was localized within the plastids and proved to be involved in the degradation of starch granules in the organelles of rice cells. In addition, a large portion of transiently expressed AmyI-1 fused to green fluorescent protein (AmyI-1-GFP) colocalized with a simultaneously expressed fluorescent plastid marker in onion (Allium cepa) epidermal cells. The plastid targeting of AmyI-1 was inhibited by both dominant-negative and constitutively active mutants of Arabidopsis thaliana ARF1 and Arabidopsis SAR1, which arrest endoplasmic reticulum-to-Golgi traffic. In cells expressing fluorescent trans-Golgi and plastid markers, these fluorescent markers frequently colocalized when coexpressed with AmyI-1. Three-dimensional time-lapse imaging and electron microscopy of high-pressure frozen/freeze-substituted cells demonstrated that contact of the Golgi-derived membrane vesicles with cargo and subsequent absorption into plastids occur within the cells. The transient expression of a series of C-terminal-truncated AmyI-1-GFP fusion proteins in the onion cell system showed that the region from Trp-301 to Gln-369 is necessary for plastid targeting of AmyI-1. Furthermore, the results obtained by site-directed mutations of Trp-302 and Gly-354, located on the surface and on opposite sides of the AmyI-1 protein, suggest that multiple surface regions are necessary for plastid targeting. Thus, Golgi-to-plastid traffic appears to be involved in the transport of glycoproteins to plastids and plastid targeting seems to be accomplished in a sorting signal–dependent manner. 相似文献
39.
Identification and characterization of subpopulations in undifferentiated ES cell culture 总被引:4,自引:0,他引:4
Toyooka Y Shimosato D Murakami K Takahashi K Niwa H 《Development (Cambridge, England)》2008,135(5):909-918
Embryonic stem (ES) cells are pluripotent cells derived from the inner cell mass (ICM) and the epiblast, and have been suggested to be a homogeneous population with characteristics intermediate between them. These cells express Oct3/4 and Rex1 genes, which have been used as markers to indicate the undifferentiated state of ES cells. Whereas Oct3/4 is expressed in totipotent and pluripotent cells in the mouse life cycle, Rex1 expression is restricted to the ICM, and is downregulated in pluripotent cell populations in the later stages, i.e. the epiblast and primitive ectoderm (PrE). To address whether ES cells comprise a homogeneous population equivalent to a certain developmental stage of pluripotent cells or a heterogeneous population composed of cells corresponding to various stages of differentiation, we established knock-in ES cell lines in which genes for fluorescent proteins were inserted into the Rex1 and Oct3/4 gene loci to visualize the expression of these genes. We found that undifferentiated ES cells included at least two different populations, Rex1(+)/Oct3/4(+) cells and Rex1(-)/Oct3/4(+) cells. The Rex1(-)/Oct3/4(+) and Rex1(+)/Oct3/4(+) populations could convert into each other in the presence of LIF. In accordance with our assumption that Rex1(+)/Oct3/4(+) cells and Rex1(-)/Oct3/4(+) cells have characteristics similar to those of ICM and early-PrE cells, Rex1(+)/Oct3/4(+) cells predominantly differentiated into primitive ectoderm and contributed to chimera formation, whereas Rex1(-)/Oct3/4(+) cells differentiated into cells of the somatic lineage more efficiently than non-fractionated ES cells in vitro and showed poor ability to contribute to chimera formation. These results confirmed that undifferentiated ES cell culture contains subpopulations corresponding to ICM, epiblast and PrE. 相似文献
40.