Hachioji, Japan

Tokyo University of Pharmacy and Life science is a private university in Hachioji, Tokyo, Japan. The precursor of the school was founded in 1880 by Masataka Fujita, and it was chartered as a university in 1949. The school of Life science was established in 1994. Wikipedia.

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Chen Y.M.,University of Washington | Kikkawa Y.,Tokyo University of Pharmacy and Life Science | Miner J.H.,University of Washington
Journal of the American Society of Nephrology | Year: 2011

Laminin β2 is a component of laminin-521, which is an important constituent of the glomerular basement membrane (GBM). Null mutations in laminin β2 (LAMB2) cause Pierson syndrome, a severe congenital nephrotic syndrome with ocular and neurologic defects. In contrast, patients with LAMB2 missense mutations, such as R246Q, can have less severe extrarenal defects but still exhibit congenital nephrotic syndrome. To investigate how such missense mutations in LAMB2 cause proteinuria, we generated three transgenic lines of mice in which R246Q-mutant rat laminin β2 replaced the wild-type mouse laminin β2 in the GBM. These transgenic mice developed much less severe proteinuria than their nontransgenic Lamb2-deficient littermates; the level of proteinuria correlated inversely with R246Q-LAMB2 expression. At the onset of proteinuria, expression and localization of proteins associated with the slit diaphragm and foot processes were normal, and there were no obvious ultrastructural abnormalities. Low transgene expressors developed heavy proteinuria, foot process effacement, GBM thickening, and renal failure by 3 months, but high expressors developed only mild proteinuria by 9 months. In vitro studies demonstrated that the R246Q mutation results in impaired secretion of laminin. Taken together, these results suggest that the R246Q mutation causes nephrotic syndrome by impairing secretion of laminin-521 from podocytes into the GBM; however, increased expression of the mutant protein is able to overcome this secretion defect and improve glomerular permselectivity. Copyright © 2011 by the American Society of Nephrology.

Kaboudin B.,Institute for Advanced Studies in Basic Sciences | Mostafalu R.,Institute for Advanced Studies in Basic Sciences | Yokomatsu T.,Tokyo University of Pharmacy and Life Science
Green Chemistry | Year: 2013

We report here on the preparation of an efficient, easily recoverable and reusable Fe3O4 magnetic nanoparticle-supported Cu(ii)-β-cyclodextrin complex catalyst for the synthesis of symmetrical biaryls and 1,2,3-triazoles from arylboronic acids. The presented Fe 3O4 magnetic nanoparticle-supported Cu(ii)-β- cyclodextrin complex catalyst was characterized by TEM, XRD, VSM, TGA, and FT-IR spectrometer. By using the catalyst, we have developed an efficient protocol for the homocoupling of aryl boronic acids for the synthesis of biaryls. The catalyst is also active in the synthesis of 1,2,3-triazoles via a one-pot reaction of an arylboronic acid with sodium azide in water followed by a click cyclization reaction with an alkyne at room temperature in air without any additives. The reusability of the prepared nanocatalyst was successfully examined four times with only a very slight loss of catalytic activity. © 2013 The Royal Society of Chemistry.

Inoue K.,Tokyo University of Pharmacy and Life Science | Yuasa H.,Nagoya City University
Drug Metabolism and Pharmacokinetics | Year: 2014

Methotrexate (MTX) is a derivative of folic acid (folate) and commonly used as an anchor drug for the treatment of rheumatoid arthritis (RA). The pharmacokinetics (PK) and pharmacodynamics (PD) of MTX entirely depends on the function of specific transporters that belong to the two major superfamilies, solute carrier transporters and ATP-binding cassette transporters. Several transporters have been identified as being able to mediate the transport of MTX, and suggested to be involved in the disposition in the body and in the regulation of intracellular metabolism in target cells, together with several enzymes involved in folate metabolism. Thus, drug-drug interactions through the transporters and their genetic polymorphisms may alter the PK and PD of MTX, resulting in an interpatient variability of efficacy. This review summarizes the PK and PD of MTX, particularly in relation to RA therapy and focuses on the roles of transporters involved in PK and PD with the aim of facilitating an understanding of the molecular basis of the mechanism of MTX action to achieve its effective use in RA therapy. Copyright © 2014 by the Japanese Society for the Study of Xenobiotics (JSSX).

Yamada Y.,Tokyo University of Pharmacy and Life Science
Biopolymers | Year: 2010

Laminin active peptide-conjugated chitosan mambranes have been previously demonstrated as a useful biomaterial for tissue engineering. Here, three laminin active peptides, A99 (AGTFALRGDNPQG), AG73 (RKRLQVQLSIRT), and EF1zz (ATLQLQEGRLHFXFDLGKGR, X: Nle), which interact with integrin αvβ3, syndecans, and integrin α2β1, respectively, were conjugated to alginate and evaluated the biological activities. A99-alginate (3-3000 ng/mm(2)) promoted cell attachment depending on the amount of alginate. More than 300 ng/mm(2) of the A99-alginate matrices effectively promoted cell attachment, cell spreading with well-organized actin stress fibers, and neurite outgrowth. AG73- and EF1zz-alginates promoted strong cell attachment at the all amounts (3-3000 ng/mm(2)). A99-alginate (30-3000 ng/mm(2)) promoted strong neurite outgrowth but lower amounts of A99-alginate (3 ng/mm(2)) showed weak activity. In contrast, AG73-alginates (3-30 ng/mm(2)) showed strong neurite outgrowth activity but higher amounts of AG73-alginate (300-3000 ng/mm(2)) decreased the activity. These data indicate that neurite outgrowth activity of peptide-alginate matrices is peptide specific and the activity is dependent on the amount of alginate. Further, biological activities of the peptides on alginate and chitosan matrices were different, suggesting that the integrin- and syndecan-mediated cellular functions on the peptide-matrices are highly influenced by the scaffold structure including polysaccharide types and amounts. The laminin active peptide-conjugated alginate and chitosan matrices can control receptor type specific functions and are useful for tissue engineering. 2010 Wiley Periodicals, Inc.

Hayakawa M.,Tokyo University of Pharmacy and Life Science
Journal of Biochemistry | Year: 2012

Nuclear factor-κB (NF-κB) is a master regulator of immunity and also involved in malignant transformation. It has been widely accepted that Lys-48 (K48)-linked polyubiquitination plays a critical role in NF-κB signalling by targeting inhibitor of NF-κB (IκB), thereby leading to its degradation by the proteasome. Alternatively, studies on IL-1 and TNF signalling have revealed that proteins modified with K63-linked polyubiquitin chains do not undergo the proteasomal degradation, instead, function as the signalling platforms required for the activation of the IκB kinase (IKK) complex. From the studies on lymphoid malignancies, human T cell leukaemia virus 1-derived protein, Tax, has been shown to activate the IKK complex, although the mechanism is largely unknown. Recently, Shibata et al. (Activation of the IκB kinase complex by HTLV-1 Tax requires cytosolic factors involved in Tax-induced polyubiquitination. J. Biochem. 150: 679-686, 2011) has established a cell free IKK assay system and demonstrated that recombinant Tax protein can activate the IKK complex in a K63-linked-polyubiquitination-dependent manner. This cell free assay system will be useful for the identification of various key players responsible for Tax-induced IKK activation. The Authors 2011. Published by Oxford University Press on behalf of the Japanese Biochemical Society. © The Authors 2011. Published by Oxford University Press on behalf of the Japanese Biochemical Society. All rights reserved.

Yanai H.,Tokyo University of Pharmacy and Life Science | Taguchi T.,Tokyo University of Pharmacy and Life Science
European Journal of Organic Chemistry | Year: 2011

Fluoro-olefin compounds, because of their favorable physicochemical properties, have been used as key materials in the fields of medicinal chemistry, chemical biology, and materials sciences. A number of the synthetic methodologies for applications of fluoro-olefin compounds were developed simultaneously. This review article provides an overview not only of recent progress in syntheses of fluoro-olefin compounds but also of some classical but still valuable synthetic reactions. Fluoro-olefins have been used as key functionalities to provide biologically active compounds such as enzyme inhibitors, peptide mimetics, and antibiotics. This review provides an overview not only of recent progress in syntheses of fluoro-olefin compounds but also of some classical but still valuable synthetic reactions. © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Arasaki K.,Yale University | Arasaki K.,Tokyo University of Pharmacy and Life Science | Toomre D.K.,Yale University | Roy C.R.,Yale University
Cell Host and Microbe | Year: 2012

The intracellular bacterial pathogen Legionella pneumophila subverts host membrane transport pathways to promote fusion of vesicles exiting the endoplasmic reticulum (ER) with the pathogen-containing vacuole. During infection there is noncanonical pairing of the SNARE protein Sec22b on ER-derived vesicles with plasma membrane (PM)-localized syntaxin proteins on the vacuole. We show that the L. pneumophila Rab1-targeting effector DrrA is sufficient to stimulate this noncanonical SNARE association and promote membrane fusion. DrrA activation of the Rab1 GTPase on PM-derived organelles stimulated the tethering of ER-derived vesicles with the PM-derived organelle, resulting in vesicle fusion through the pairing of Sec22b with the PM syntaxin proteins. Thus, the effector protein DrrA stimulates a host membrane transport pathway that enables ER-derived vesicles to remodel a PM-derived organelle, suggesting that Rab1 activation at the PM is sufficient to promote the recruitment and fusion of ER-derived vesicles. © 2012 Elsevier Inc.

Zhao Y.,University of Tokyo | Watanabe K.,University of Tokyo | Watanabe K.,Tokyo University of Pharmacy and Life Science | Hashimoto K.,University of Tokyo
Journal of the American Chemical Society | Year: 2012

We report the design, synthesis, and evaluation of a new type of non-precious-metal catalyst made from network polymers. 2,6-Diaminopyridine was selected as a building-block monomer for the formation of a nitrogen-rich network polymer that forms self-supporting spherical backbone structures and contains a high density of metal-coordination sites. A Co-/Fe-coordinating pyrolyzed polymer exhibited a high specific oxygen reduction activity with onset and half-wave potentials of 0.87 and 0.76 V vs RHE, respectively, in neutral media. There was no crossover effect of organics on its activity. The power output of a microbial fuel cell equipped with this catalyst on its cathode was more than double the output with a commercial 20 wt % Pt/C catalyst. © 2012 American Chemical Society.

Yanai H.,Tokyo University of Pharmacy and Life Science | Taguchi T.,Tokyo University of Pharmacy and Life Science
Chemical Communications | Year: 2012

(Z)-Selective olefination of several lactones with ketene silyl acetals was achieved by the catalysis of carbon acids (C-H acids) having a bis(triflyl)methyl group as an acidic functionality; in particular, the triple carbon acid having three bis(triflyl)methyl groups in phloroglucinol shows an excellent catalytic performance. © 2012 The Royal Society of Chemistry.

University of Tokyo, Tokyo University of Pharmacy and Life Science | Date: 2014-11-16

A method and evaluation kit are provided, in which a high-capacity urate transporter is identified to assist in the early treatment and prevention of urate transport-related disease and inflammation-related disease. The method can include a step for detecting variations in genes that encode ABCG2 protein. When a subject has an SNP of V12M, R113X, Q126X, Q141K, F2085, G268R, E334X, S441N, L447V, S486N, F506SfsX4, R575X, and/or C608X, it can be concluded that the subject has a factor that is capable of inducing urate transport failure, or a state or disease attributable to that failure. When a subject has an SNP of V12M, it can be concluded that, unlike the other SNPs, there is a possibility that the subject does not possess such a factor because, although this variation itself does not lead to a change in urate transport capability, said variation is related to linkage disequilibrium with other SNPs.

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