Abstract:
:As a new strategy for drug discovery and development, I focus on drug re-profiling as a way to identify new treatments for diseases. In this strategy, the actions of existing medicines, whose safety and pharmacokinetic effects in humans have already been confirmed clinically and approved for use, are examined comprehensively at the molecular level and the results used for the development of new medicines. This strategy is based on the fact that we still do not understand the underlying mechanisms of action of many existing medicines, and as such the cellular responses that give rise to their main effects and side effects are yet to be elucidated. To this extent, identification of the mechanisms underlying the side effects of medicines offers a means for us to develop safer drugs. The results can also be used for developing existing drugs for use as medicines for the treatment of other diseases. Promoting this research strategy could provide breakthroughs in drug discovery and development.
journal_name
J Biochemjournal_title
Journal of biochemistryauthors
Mizushima Tdoi
10.1093/jb/mvr032subject
Has Abstractpub_date
2011-05-01 00:00:00pages
499-505issue
5eissn
0021-924Xissn
1756-2651pii
mvr032journal_volume
149pub_type
杂志文章abstract::Photoaffinity labeling with [3H]cytochalasin B detects two D-glucose-sensitive proteins in the chicken embryo fibroblast (CEF) plasma membrane, which accumulate under conditions of glucose starvation and are probably involved in the glucose transport system (Pessin, J.E., et al. (1982) Proc. Natl. Acad. Sci. U.S. 79, ...
journal_title:Journal of biochemistry
pub_type: 杂志文章
doi:10.1093/oxfordjournals.jbchem.a135458
更新日期:1986-01-01 00:00:00
abstract::The purpose of this study was to determine whether ATP-sensitive potassium channel (K(ATP) channel) activation generates oxygen free radicals in the rabbit heart. We assayed malondialdehyde (MDA) in rabbit heart slices in vitro as an indicator of oxygen free radical generation. The K(ATP) channel openers, pinacidil an...
journal_title:Journal of biochemistry
pub_type: 杂志文章
doi:10.1093/oxfordjournals.jbchem.a003157
更新日期:2002-05-01 00:00:00
abstract::Fluorescence resonance energy transfer spectroscopy has been used to study the spatial relationships between probes attached to actin and troponin in the reconstituted skeletal muscle thin filament in the presence and absence of Ca2+ ions. Gln-41 and the nucleotide-binding site of actin were selectively labeled with t...
journal_title:Journal of biochemistry
pub_type: 杂志文章
doi:10.1093/oxfordjournals.jbchem.a021940
更新日期:1998-02-01 00:00:00
abstract::Ca2+-Activated neutral protease (CANP), that consists of 80K and 30K subunits, is converted to a low-Ca2+-requiring form by autolysis in the presence of Ca2+. Phosphatidylinositol greatly reduces the Ca2+-requirement for the autolysis of native CANP. However, this effect was not observed for CANP with a trimmed 30K su...
journal_title:Journal of biochemistry
pub_type: 杂志文章
doi:10.1093/oxfordjournals.jbchem.a135593
更新日期:1986-04-01 00:00:00
abstract::The functions of the helix E (W97-F105), an amphiphilic lumenal 310 helix of the major antenna of photosystem II (LHCII), are still unidentified. To elucidate the roles of individual amino acid residue of the helix E, alanine scanning mutagenesis has been performed to mutate every residue of this domain to alanine. Th...
journal_title:Journal of biochemistry
pub_type: 杂志文章
doi:10.1093/jb/mvu028
更新日期:2014-10-01 00:00:00
abstract::Heat-stable L-lactate dehydrogenase [EC 1.1.1.27] was purified from an extremely thermophilic bacterium belonging to the genus Thermus, and it showed an allosteric nature dependent on fructose 1,6-bisphosphate as an effector. The enzyme had a molecular weight of approximately 120,000 with a subunit molecular weight of...
journal_title:Journal of biochemistry
pub_type: 杂志文章
doi:10.1093/oxfordjournals.jbchem.a133821
更新日期:1982-04-01 00:00:00
abstract::N-acylethanolamines (NAEs) are a class of bioactive lipid molecules in animal tissues, including the endocannabinoid anandamide and the anti-inflammatory substance N-palmitoylethanolamine. Enzymatic hydrolysis of NAEs is considered to be an important step to regulate their endogenous levels. Lysosomal NAE-hydrolysing ...
journal_title:Journal of biochemistry
pub_type: 杂志文章
doi:10.1093/jb/mvn122
更新日期:2008-11-01 00:00:00
abstract::Cucumisin was isolated from prince melon sarcocarp by means of a simple purification procedure. Serine protease inhibitors such as soybean trypsin inhibitor, ovomucoid, and aprotinin had no effect on the enzyme activity. alpha 2-Macroglobulin showed 38% inhibition of the original caseinolytic activity of cucumisin. Th...
journal_title:Journal of biochemistry
pub_type: 杂志文章
doi:10.1093/oxfordjournals.jbchem.a124817
更新日期:1995-05-01 00:00:00
abstract::2-Amino-4-methylphenol was converted to a brownish yellow material by the lysates of human erythrocytes or purified human hemoglobin. The reaction proceeded oxidatively, coupled with the oxidation of hemoglobin. The major component of the brownish yellow material produced by oxidative condensation of 2-amino-4-methylp...
journal_title:Journal of biochemistry
pub_type: 杂志文章
doi:10.1093/oxfordjournals.jbchem.a123669
更新日期:1991-12-01 00:00:00
abstract::The 5'-AMP-activated protein kinase (AMPK) functions as a cellular energy sensor. 5-Aminoimidazole-4-carboxyamide-1-β-D-ribofranoside (AICAR) is a chemical activator of AMPK. In the liver, AICAR suppresses expression of thephosphoenolpyruvate carboxykinase(PEPCK) gene. The rat enhancer of split- and hairy-related prot...
journal_title:Journal of biochemistry
pub_type: 杂志文章
doi:10.1093/jb/mvv116
更新日期:2016-04-01 00:00:00
abstract::Long interspersed nuclear element (LINE) is known to be transposed by reverse transcription using its RNA transcript. Recognition of the 3' stem-loop of LINE RNA by its reverse transcriptase (RT) is an important step of the retrotransposition. Our previous study revealed that the second G residue (G8) in the GGAUA loo...
journal_title:Journal of biochemistry
pub_type: 杂志文章
doi:10.1093/jb/mvx026
更新日期:2017-10-01 00:00:00
abstract::The steric course of the enoyl reduction catalyzed by fatty acid synthetase was investigated with the enzymes from bakers' yeast, rat liver and Brevibacterium ammoniagenes. The non-enzymic hydrogen-deuterium exchange of the methylene group of malonyl-CoA was studied by NMR spectroscopy. The half-life period of the met...
journal_title:Journal of biochemistry
pub_type: 杂志文章
doi:10.1093/oxfordjournals.jbchem.a133646
更新日期:1981-12-01 00:00:00
abstract::Midkine (MK) is a 13-kDa heparin-binding growth/differentiation factor, and its interaction with heparan sulfate proteoglycan is important in promotion of neurite outgrowth. This study was performed to reveal the species of syndecans that interact with MK during embryogenesis of the central nervous system in the rat. ...
journal_title:Journal of biochemistry
pub_type: 杂志文章
doi:
更新日期:1997-02-01 00:00:00
abstract::Rho-kinase is a main player in the regulation of cytoskeletal events and a promising drug target in the treatment of both vascular and neurological disorders. Here we report the crystal structure of the Rho-kinase catalytic domain in complex with the specific inhibitor Y-27632. Comparison with the structure of PKA bou...
journal_title:Journal of biochemistry
pub_type: 杂志文章
doi:10.1093/jb/mvj172
更新日期:2006-09-01 00:00:00
abstract::Streptomyces caespitosus neutral protease (ScNP) is one of the smallest metalloproteinase with a molecular mass of 14 kDa. Effects of solvent composition on ScNP activity were examined using a peptide substrate. The k(cat)/K(m) values of ScNP exhibited bell-shaped pH-dependence with the optimal pH of 6.4-7.0 and the p...
journal_title:Journal of biochemistry
pub_type: 杂志文章
doi:10.1093/jb/mvm134
更新日期:2007-09-01 00:00:00
abstract::The genomic organization of the gene encoding the human adipocyte-derived leucine aminopeptidase (A-LAP) has been determined. The gene is composed of 20 exons and 19 introns and spans approximately 47 kilobases of chromosome 5q15. The gluzincin aminopeptidase motif, the HEXXH(X)(18)E zinc-binding motif essential for e...
journal_title:Journal of biochemistry
pub_type: 杂志文章
doi:10.1093/oxfordjournals.jbchem.a002977
更新日期:2001-08-01 00:00:00
abstract::The planar cell polarity (PCP) protein, Prickle (Pk), is conserved in invertebrates and vertebrates, and regulates cellular morphogenesis and movement. Vertebrate Pk consists of at least two family members, Pk1 and Pk2, both of which are expressed in the brain; however, their localization and function at synapses rema...
journal_title:Journal of biochemistry
pub_type: 杂志文章
doi:10.1093/jb/mvr023
更新日期:2011-06-01 00:00:00
abstract::Nestin is an intermediate filament protein mainly expressed in muscle and neural progenitors. Recently, we reported that nestin is expressed in rat vascular smooth muscle cells (VSMCs), disappears after serum-deprivation and then is re-expressed again following EGF stimulation. As the function of nestin in VSMCs remai...
journal_title:Journal of biochemistry
pub_type: 杂志文章
doi:10.1093/jb/mvp070
更新日期:2009-09-01 00:00:00
abstract::It is well established that promyelocytic leukaemia nuclear bodies (PML NBs) play important roles in DNA damage responses (DDR). After irradiation, PML NBs dynamically recruit or release important proteins involved in cell-cycle regulation, DNA repair and apoptosis. As PML protein is the key molecule of PML NBs' dynam...
journal_title:Journal of biochemistry
pub_type: 杂志文章
doi:10.1093/jb/mvq105
更新日期:2010-12-01 00:00:00
abstract::We found functionally active thrombomodulin in human platelets (60 +/- 18 molecules per platelet). Protein C appeared not to be activated by thrombin with gel-filtered platelets. However, the activation of protein C by thrombin was accelerated by thrombin-stimulated and washed platelets. This cofactor activity of the ...
journal_title:Journal of biochemistry
pub_type: 杂志文章
doi:10.1093/oxfordjournals.jbchem.a122523
更新日期:1988-10-01 00:00:00
abstract::The biosynthesis of elongation factor Tu (EF-Tu) has been studied in a cell-free system with DNA of the transducing phage lambdarifd18 as a template. It was found that the synthesis of EF-Tu in this system was inhibited by about 60% in the presence of 0.3 to 0.6 mM guanosine-5'-diphosphate-3'-diphosphate (ppGpp). The ...
journal_title:Journal of biochemistry
pub_type: 杂志文章
doi:10.1093/oxfordjournals.jbchem.a132539
更新日期:1979-08-01 00:00:00
abstract::EnvZ is a membrane-located protein kinase which modulates expression of the ompF and ompC genes through phosphotransfer signal transduction in Escherichia coli. Previously, we developed an in vitro method for analyzing the intact form of EnvZ in isolated cytoplasmic membranes, and demonstrated that this particular for...
journal_title:Journal of biochemistry
pub_type: 杂志文章
doi:10.1093/oxfordjournals.jbchem.a123823
更新日期:1992-06-01 00:00:00
abstract::Candida albicans is a commensal organism, but causes life-threatening infections in immunocompromised patients. Certain factors such as yeast-hyphae transition and hydrolytic enzymes are suggested as virulence attributes of C. albicans. Among them, 10 types of secreted aspartic protease (SAP) genes have received parti...
journal_title:Journal of biochemistry
pub_type: 杂志文章
doi:10.1093/jb/mvr073
更新日期:2011-10-01 00:00:00
abstract::OsGEN-L has a 5'-flap endonuclease activity and plays an essential role in rice microspore development. The Class 4 RAD2/XPG family nucleases, including OsGEN-L, were recently found to have resolving activity for the Holliday junction (HJ), the intermediate of DNA strand recombination. In this study, we performed a de...
journal_title:Journal of biochemistry
pub_type: 杂志文章
doi:10.1093/jb/mvr145
更新日期:2012-03-01 00:00:00
abstract::Protein S, a vitamin K-dependent plasma protein having Gla-residues, increases the rate of inactivation of Factor Va by activated protein C by enhancing the binding of activated protein C to phospholipid [Walker, J.F. (1981) J. Biol. Chem. 256, 11128-11131]. The present study aimed at elucidating the effect of thrombi...
journal_title:Journal of biochemistry
pub_type: 杂志文章
doi:10.1093/oxfordjournals.jbchem.a134409
更新日期:1983-09-01 00:00:00
abstract::Steroid monooxygenase of Rhodococcus rhodochrous is a Baeyer-Villigerase catalyzing the insertion of an oxygen atom between the C(17)- and C(20)-carbons of progesterone to produce testosterone acetate. The 5.1-kbp-long BamHI DNA fragment containing the steroid monooxygenase gene, smo, was cloned from the chromosomal D...
journal_title:Journal of biochemistry
pub_type: 杂志文章
doi:10.1093/oxfordjournals.jbchem.a022494
更新日期:1999-09-01 00:00:00
abstract::Homogeneous indanol dehydrogenase from monkey liver catalyzed the reversible conversion of 3 alpha- or 20 alpha-hydroxy groups of several bile acids and 5 beta-pregnanes to the corresponding 3- or 20-ketosteroids. The kcat values for the steroids determined at pH 7.4 were low, but the kcat/Km values for the 3-ketoster...
journal_title:Journal of biochemistry
pub_type: 杂志文章
doi:10.1093/oxfordjournals.jbchem.a122949
更新日期:1989-11-01 00:00:00
abstract::Inhibitory PAS domain protein (IPAS) is a dual function protein acting as a transcriptional repressor and as a pro-apoptotic protein. Simultaneous dual-color single-molecule imaging of EGFP-IPAS coexpressed with Mit-TagRFP-T in living HeLa cells revealed that fraction of EGFP-IPAS was arrested in the nucleus and on mi...
journal_title:Journal of biochemistry
pub_type: 杂志文章
doi:10.1093/jb/mvw068
更新日期:2017-03-01 00:00:00
abstract::Sulfation of glycosaminoglycans (GAGs) secreted by baby hamster kidney (BHK) cells and the polyoma virus-transformants (PY-BHK) was investigated. It has been reported that chondroitin sulfate (CS) of cell membranes from PY-BHK cells is undersulfated compared to that from BHK cells (Cancer Res. 43, 2712-2717, 1983). In...
journal_title:Journal of biochemistry
pub_type: 杂志文章
doi:10.1093/oxfordjournals.jbchem.a135367
更新日期:1985-10-01 00:00:00
abstract::Temperature and solvent effects on reaction center structures were examined in two thermophilic photosynthetic bacteria, Chloroflexus aurantiacus and Chromatium tepidum, in order to gain insight into the interactions among the reaction center proteins and pigment systems. Thermal stability of the reaction centers was ...
journal_title:Journal of biochemistry
pub_type: 杂志文章
doi:10.1093/oxfordjournals.jbchem.a123624
更新日期:1991-10-01 00:00:00