Updated on 2024/02/01

写真a

 
Kusano Teruo
 
Affiliation
Faculty of Medicine, Department of Biochemistry and Molecular Biology, Assistant Professor
Title
Assistant Professor
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Research Interests

  • タンパク質コンフォメーション変換

  • 金属タンパク質

  • キサンチン酸化還元酵素

  • Reactive oxygen species

  • ヘムタンパク質

  • ラクトペルオキシダーゼ

  • metabolism

  • Molecular biology

  • Biochemistry

Research Areas

  • Life Science / Medical biochemistry

  • Life Science / Pathological biochemistry

  • Life Science / Molecular biology

Research History

  • Nippon Medical School   Assistant Professor

    2006.4

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  • Nippon Medical School

    2001.4 - 2006.3

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Papers

  • The mechanism and significance of the conversion of xanthine dehydrogenase to xanthine oxidase in mammalian secretory gland cells Reviewed

    Teruo Kusano, Tomoko Nishino, Ken Okamoto, Russ Hille, Takeshi Nishino

    Redox Biol   59   102573   2023.2

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    Authorship：Lead author   Language：English  

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  • Xanthine Oxidoreductase Is Involved in Chondrocyte Mineralization and Expressed in Osteoarthritic Damaged Cartilage. Reviewed International journal

    Sonia Nasi, Mariela Castelblanco, Véronique Chobaz, Driss Ehirchiou, Alexander So, Ilaria Bernabei, Teruo Kusano, Takeshi Nishino, Ken Okamoto, Nathalie Busso

    Frontiers in cell and developmental biology   9   612440 - 612440   2021

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    Language：English   Publishing type：Research paper (scientific journal)  

    Pathologic calcification of cartilage consists of the formation of basic calcium phosphate (BCP) and/or calcium pyrophosphate dihydrate (CPPD) containing calcium crystals in mature hyaline or articular cartilage and is associated with aging, cartilage injury and likely plays a role in accelerating the pathology of osteoarthritis (OA). The pathways regulating joint calcification, in particular cartilage calcification, are not completely understood, but inflammation and the formation of reactive oxygen species (ROS) are contributory factors. The xanthine oxidase (XO) form of xanthine oxidoreductase (XOR), the key enzyme in xanthine and uric acid metabolism, is a major cellular source of superoxide. We hypothesized that XOR could be implicated in chondrocyte mineralization and cartilage calcification and degradation in OA. We showed both in murine primary chondrocyte and chondrogenic ATDC5 cells, that mineralization was inhibited by two different XOR inhibitors, febuxostat and allopurinol. In addition, XOR inhibition reduced the expression of the pro-mineralizing cytokine interleukin-6 (IL-6). We next generated XOR knock-out chondrocyte cell lines with undetectable XOR expression and XO activity. XOR knock-out chondrocyte cells showed decreased mineralization and reduced alkaline phosphatase (Alp) activity. To assess the precise form of XOR involved, primary chondrocytes of XOR mutant mice expressing either the XDH form (XDH ki) or the XO form (XO ki) were studied. We found that XO ki chondrocytes exhibited increased mineralization compared to XDH ki chondrocytes, and this was associated with enhanced Alp activity, ROS generation and IL-6 secretion. Finally, we found increased XOR expression in damaged vs. undamaged cartilage obtained from OA patients and XOR expression partially co-localized with areas showing pathologic calcification. Altogether, our results suggest that XOR, via its XO form, contribute to chondrocyte mineralization and pathological calcification in OA cartilage.

    DOI： 10.3389/fcell.2021.612440

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  • Targeted knock-in mice expressing the oxidase-fixed form of xanthine oxidoreductase favor tumor growth. Reviewed International journal

    Kusano T, Ehirchiou D, Matsumura T, Chobaz V, Nasi S, Castelblanco M, So A, Lavanchy C, Acha-Orbea H, Nishino T, Okamoto K, Busso N

    Nature communications   10 ( 1 )   4904   2019.10

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    Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)  

    Xanthine oxidoreductase has been implicated in cancer. Nonetheless, the role played by its two convertible forms, xanthine dehydrogenase (XDH) and oxidase (XO) during tumorigenesis is not understood. Here we produce XDH-stable and XO-locked knock-in (ki) mice to address this question. After tumor transfer, XO ki mice show strongly increased tumor growth compared to wild type (WT) and XDH ki mice. Hematopoietic XO expression is responsible for this effect. After macrophage depletion, tumor growth is reduced. Adoptive transfer of XO-ki macrophages in WT mice increases tumor growth. In vitro, XO ki macrophages produce higher levels of reactive oxygen species (ROS) responsible for the increased Tregs observed in the tumors. Blocking ROS in vivo slows down tumor growth. Collectively, these results indicate that the balance of XO/XDH plays an important role in immune surveillance of tumor development. Strategies that inhibit the XO form specifically may be valuable in controlling cancer growth.

    DOI： 10.1038/s41467-019-12565-z

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  • New Strategy That Delays Progression of Amyotrophic Lateral Sclerosis in G1H-G93A Transgenic Mice: Oral Administration of Xanthine Oxidoreductase Inhibitors That Are Not Substrates for the Purine Salvage Pathway Reviewed

    Shinsuke Kato, Masako Kato, Teruo Kusano, Takeshi Nishino

    JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY   75 ( 12 )   1124 - 1144   2016.12

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    Language：English   Publishing type：Research paper (scientific journal)   Publisher：OXFORD UNIV PRESS INC  

    Amyotrophic lateral sclerosis (ALS), Lou Gehrig's disease, is a progressive fatal neurodegenerative disease that involves both upper and lower motor neurons. We orally administered 4 xanthine oxido-reductase (XOR) inhibitors to G1H-G93A mice carrying 25 transgene copy numbers of human mutant G93A superoxide dismutase 1, from 80 days of age. Three nonpurine-analogue inhibitors (TEI-6720: Febuxostat, Y-700 and FYX-051), but not allopurinol with a purine analogue ring (pyrazolo pyrimidine ring), significantly delayed disease onset, prolonged survival and the duration of disease stages, improved clinical signs, and alleviated weight loss. Exercise testing (extension reflex, inclined plane, footprint, rotarod, and beam balance tests) showed significantly improved motor function in the G1H-G93A mice treated with these 3 inhibitors. Significant amelioration of disease was seen even when TEI-6720 or Y-700 was administered after the appearance of early signs. Histopathological evaluation in the late stage revealed that G1H-G93A mice treated with TEI-6720 had well-preserved motor neurons and fewer inclusion bodies, compared with mice treated with placebo or with allopurinol. Our results indicate that these 3 nonpurine-analogue XOR inhibitors might increase the supply of high-energy compounds via the purine salvage pathway, thereby protecting motor neurons against death. This strategy may be applicable for oral therapy of ALS patients.

    DOI： 10.1093/jnen/nlw088

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  • The Effects of Xanthine Oxidoreductase Inhibitors on Oxidative Stress Markers following Global Brain Ischemia Reperfusion Injury in C57BL/6 Mice Reviewed

    Masahiro Yamaguchi, Ken Okamoto, Teruo Kusano, Yoko Matsuda, Go Suzuki, Akira Fuse, Hiroyuki Yokota

    PLOS ONE   10 ( 7 )   e0133980   2015.7

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    Language：English   Publishing type：Research paper (scientific journal)   Publisher：PUBLIC LIBRARY SCIENCE  

    We demonstrated that 3-nitrotyrosine and 4-hydroxy-2-nonenal levels in mouse brain were elevated from 1 h until 8 h after global brain ischemia for 14 min induced with the 3-vessel occlusion model; this result indicates that ischemia reperfusion injury generated oxidative stress. Reactive oxygen species production was observed not only in the hippocampal region, but also in the cortical region. We further evaluated the neuroprotective effect of xanthine oxidoreductase inhibitors in the mouse 3-vessel occlusion model by analyzing changes in the expression of genes regulated by the transcription factor nuclear factor-kappa B (including pro-inflammatory cytokines interleukin-1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF-alpha), matrix metalloproteinase-9 and intercellular adhesion molecules-1). Administration of allopurinol resulted in a statistically significant decrease in IL-1 beta and TNF-alpha mRNA expression, whereas febuxostat had no significant effect on expression of these genes; nevertheless, both inhibitors effectively reduced serum uric acid concentration. It is suggested that the neuroprotective effect of allopurinol is derived not from inhibition of reactive oxygen species production by xanthine oxidoreductase, but rather from a direct free-radical-scavenging effect.

    DOI： 10.1371/journal.pone.0133980

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  • Evaluation of Neuronal Protective Effects of Xanthine Oxidoreductase Inhibitors on Severe Whole-brain Ischemia in Mouse Model and Analysis of Xanthine Oxidoreductase Activity in the Mouse Brain Reviewed

    Go Suzuki, Ken Okamoto, Teruo Kusano, Yoko Matsuda, Akira Fuse, Hiroyuki Yokota

    NEUROLOGIA MEDICO-CHIRURGICA   55 ( 1 )   77 - 85   2015.1

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    Language：English   Publishing type：Research paper (scientific journal)   Publisher：JAPAN NEUROSURGICAL SOC  

    Global cerebral ischemia and reperfusion (I/R) often result in high mortality. Free radicals play an important role in global cerebral I/R. Xanthine oxidoreductase (XOR) inhibitors, such as allopurinol, have been reported to protect tissues from damage caused by reactive oxygen species (ROS) by inhibiting its production through XOR inhibition. The recently introduced XOR inhibitor febuxostat, which is a more potent inhibitor than allopurinol, is expected to decrease free radical production more effectively. Here, we analyzed the effects of allopurinol and febuxostat in decreasing global severe cerebral I/R damage in mice. Mice were divided into three groups: a placebo group, an allopurinol group, and a febuxostat group. Pathological examinations, which were performed in each group in the CA1 and CA2 regions of the hippocampus 4 days after I/R surgery, revealed that there was a decrease in the number of neuronal cells in the 14-min occlusion model in both regions and that drugs that were administered to prevent this damage were not effective. The enzymatic activity was extremely low in the mouse brain, and XOR could not be detected in the nonischemic and ischemic mice brains with western blot analyses. Thus, one of the reasons for the decreased effectiveness of XOR inhibitors in controlling severe whole-brain ischemia in a mouse model was the low levels of expression of XOR in the mouse brain.

    DOI： 10.2176/nmc.oa.2013-0307

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  • Phosphorylation of Thr(1495) of nestin in a mouse model of cerebral ischemia and reperfusion damage Reviewed

    Yoko Matsuda, Go Suzuki, Teruo Kusano, Yoko Kawamoto, Hisashi Yoshimura, Akira Fuse, Hiroyuki Yokota, Zenya Naito, Toshiyuki Ishiwata

    PATHOLOGY INTERNATIONAL   63 ( 9 )   448 - 456   2013.9

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    Language：English   Publishing type：Research paper (scientific journal)   Publisher：WILEY-BLACKWELL  

    Nestin, a class VI intermediate filament protein, is expressed by neuronal progenitor cells in the subventricular zone (SVZ). In the present study, we analyzed the nestin expression and phosphorylation levels in nerve cells in a mouse model of cerebral ischemia and reperfusion. C57BL/6 mice were subjected to three-vessel occlusion for 14min, and were killed either 1 or 4 days after the procedure. The percentages of cells in the SVZ that were positive for nestin, Thr(1495)-phosphorylated nestin or Ki67 did not significantly differ between the ischemic reperfusion and sham groups. Conversely, in the striatum and cornu ammonis 2 (CA2) regions, the mice at 4 days after ischemic reperfusion showed significantly higher numbers and percentages of nerve cells that were positive for nestin, Thr(1495)-phosphorylated nestin and Ki67 compared to results from the other groups. To our knowledge, this is the first description of phosphorylated nestin expression in neural progenitor cells in the SVZ of adult mice. In this cerebral ischemia and reperfusion mouse model, cells positive for Thr(1495)-phosphorylated nestin were increased in the striatum and CA2 field of the hippocampus; suggesting that nestin phosphorylation may play an important role in mitotically active neuronal progenitor cells.

    DOI： 10.1111/pin.12092

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  • Chemical Nature and Reaction Mechanisms of the Molybdenum Cofactor of Xanthine Oxidoreductase Reviewed

    Ken Okamoto, Teruo Kusano, Takeshi Nishino

    CURRENT PHARMACEUTICAL DESIGN   19 ( 14 )   2606 - 2614   2013.4

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    Language：English   Publishing type：Research paper (scientific journal)   Publisher：BENTHAM SCIENCE PUBL LTD  

    Xanthine oxidoreductase (XOR), a complex flavoprotein, catalyzes the metabolic reactions leading from hypoxanthine to xanthine and from xanthine to urate, and both reactions take place at the molybdenum cofactor. The enzyme is a target of drugs for therapy of gout or hyperuricemia. We review the chemical nature and reaction mechanisms of the molybdenum cofactor of XOR, focusing on molybdenum-dependent reactions of actual or potential medical importance, including nitric oxide (NO) synthesis. It is now generally accepted that XOR transfers the water-exchangeable -OH ligand of the molybdenum atom to the substrate. The hydroxyl group at OH-Mo(IV) can be replaced by urate, oxipurinol and FYX-051 derivatives and the structures of these complexes have been determined by x-ray crystallography under anaerobic conditions. Although formation of NO from nitrite or formation of xanthine from urate by XOR is chemically feasible, it is not yet clear whether these reactions have any physiological significance since the reactions are catalyzed at a slow rate even under anaerobic conditions.

    DOI： 10.2174/1381612811319140010

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  • Analysis of New Types of Covalent Linkages between Xanthine Oxidoreductase and Inhibitors.

    Okamoto K, Matsumoto K, Kawaguchi Y, Kusano T, Matsumura T, Eger TB, Pai FE, Nishino T

    FLAVINS AND FLAVOPROTEINS 2011   257 - 262   2013

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    Language：English   Publishing type：Research paper (international conference proceedings)  

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  • Genetically Modified Mouse Expressing a Xanthine Oxidase Mutant That Produces a Higher Ratio of Superoxide.

    Kusano T, Okamoto K, Matsumura T, Nishino T

    FLAVINS AND FLAVOPROTEINS 2011   245 - 250   2013

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    Authorship：Lead author   Language：English   Publishing type：Research paper (international conference proceedings)  

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  • キサンチン酸化還元酵素研究110年 第2回 酵素のプリン分解触媒機能

    草野輝男, 岡本研, 西野武士

    高尿酸血症と痛風   20 ( 1 )   92 - 97   2012.3

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    Authorship：Lead author   Language：Japanese   Publisher：(株)メディカルレビュー社  

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  • Psychrophilic Pseudomonas syringae requires trans-monounsaturated fatty acid for growth at higher temperature Reviewed

    MD Kiran, JSS Prakash, S Annapoorni, S Dube, T Kusano, H Okuyama, N Murata, S Shivaji

    EXTREMOPHILES   8 ( 5 )   401 - 410   2004.10

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    Language：English   Publishing type：Research paper (scientific journal)   Publisher：SPRINGER TOKYO  

    A psychrophilic bacterium, Pseudomonas syringae (Lz4W) from Antarctica, was used as a model system to establish a correlation, if any, between thermal adaptation, trans-fatty acid content and membrane fluidity. In addition, attempts were made to clone and sequence the cti gene of P. syringae (Lz4W) so as to establish its characteristics with respect to the cti of other Pseudomonas spp. and also to in vitro mutagenize the cti gene so as to generate a cti null mutant. The bacterium showed increased proportion of saturated and trans-monounsaturated fatty acids when grown at 28degreesC compared to cells grown at 5degreesC, and the membrane fluidity decreased with growth temperature. In the mutant. the trans-fatty acid was not synthesized, and the membrane fluidity also decreased with growth temperature, but the decrease was not to the extent that was observed in the wild-type cells. Thus, it would appear that synthesis of trans-fatty acid and modulation of membrane fluidity to levels comparable to the wild-type cells Is essential for growth at higher temperatures since the mutant exhibits growth arrest at 28degreesC. In fact, the cti null mutant-complemented strain of P. syringae (Lz4W-C30b) that was capable of synthesizing the trans-fatty acid was indeed capable of growth at 28degreesC, thus confirming the above contention. The cti gene of P. syringae (LAW) that was cloned and sequenced exhibited high sequence identity with the cti of other Pseudomonas spp. and exhibited all the conserved features.

    DOI： 10.1007/s00792-004-0401-8

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  • The factor in bovine milk and the sulfhydryl residues of xanthine oxidoreductase responsible for cnversion from dehydrogenase to oxidase forms．

    Kusano T, Nishino T, Okamoto K, Hori H, Nishino T

    FLAVINS AND FLAVOPROTEINS 2002   271 - 274   2002

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  • Assignment of Pseudomonas sp. strain E-3 to Pseudomonas psychrophila sp. nov., a new facultatively psychrophilic bacterium (vol 5, pg 343, 2001) Reviewed

    Yumoto, I, T Kusano, T Shingyo, Y Nodasaka, H Matsuyama, H Okuyama

    EXTREMOPHILES   5 ( 6 )   432 - 432   2001.12

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    Language：English   Publishing type：Research paper (scientific journal)   Publisher：SPRINGER-VERLAG TOKYO  

    DOI： 10.1007/s007920100199

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  • Purification and characterization of 9-hexadecenoic acid cis-trans isomerase from Pseudomonas sp strain E-3 Reviewed

    H Okuyama, A Ueno, D Enari, N Morita, T Kusano

    ARCHIVES OF MICROBIOLOGY   169 ( 1 )   29 - 35   1998.1

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    Authorship：Last author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：SPRINGER VERLAG  

    A 9-hexadecenoic acid cis-trans isomerase (9-isomerase) that catalyzed the cis-to-trans isomerization of the double bond of free 9-cis-hexadecenoic acid [16:1(9c)] was purified to homogeneity from an extract of Pseudomonas sp. strain E-3 and characterized. Electrophoresis of the purified enzyme on both incompletely denaturing and denaturing polyacrylamide gels yielded a single band of a protein with a molecular mass of 80 kDa, suggesting that the isomerase is a monomeric protein of 80 kDa. The 9-isomerase, assayed with 16:1(9c) as a substrate, had a specific activity of 22.8 mu mol h(-1) (mg protein)(-1) and a K-m of 117.6 mM. The optimal pH and temperature for catalysis were approximately pH 7-8 and 30 degrees C, respectively. The 9-isomerase catalyzed the cis-to-trans conversion of a double bond at positions 9, 10, or 11, but not that of a double bond at position 6 or 7 of cis-mono-unsaturated fatty acids with carbon chain lengths of 14, 15, 16, and 17. Octadecenoic acids with a double bond at position 9 or 11 were not susceptible to isomerization. These results suggest that 9-isomerase has a strict specificity for both the position of the double bond and the chain length of the fatty acid. The enzyme catalyzed the cis-to-trans isomerization of fatty acids in a free form, and in the presence of a membrane fraction it was also able to isomerize 16:1(9c) esterified to phosphatidylethanolamine. The 9-isomerase was strongly inhibited by catecholic antioxidants such as alpha-tocopherol and nordihydroguaiaretic acid, but was not inhibited by 1,10-phenanthroline or EDTA or under anoxic conditions. Based on these results, the possible mechanism. of catalysis by this enzyme is discussed.

    DOI： 10.1007/s002030050537

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  • Expression of the Escherichia coli bo-type ubiquinol oxidase with a chimeric subunit II having the Cu-A-cytochrome c domain from the thermophilic Bacillus caa(3)-type cytochrome c oxidase Reviewed

    A Uchida, T Kusano, T Mogi, Y Anraku, N Sone

    JOURNAL OF BIOCHEMISTRY   122 ( 5 )   1004 - 1009   1997.11

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    Language：English   Publishing type：Research paper (scientific journal)   Publisher：JAPANESE BIOCHEMICAL SOC  

    The C-terminal periplasmic domain of subunit II of the Escherichia cell be-type ubiquinol oxidase was replaced with the counterpart of the thermophilic Bacillus caa(3)-type cytochrome c oxidase containing the Cu-A-cytochrome c domain by means of gene engineering techniques, The chimeric terminal oxidase was expressed by a pBR322 derivative in a terminal oxidase-deficient mutant of E. coli, although the amount of the chimeric enzyme was smaller than that of the Escherichia cell be-type ubiquinol oxidase expressed by the original cytochrome be-expressing plasmid, The chimeric enzyme showed much higher TMPD (N,N,N',N' -tetramethyl-p -phenylenediamine) oxidase activity than the wild-type cytochrome be, but lower activity than the thermophilic Bacillus caa(3)-type cytochrome c oxidase, The chimeric subunit II was confirmed to bind to heme C. These results suggest that the Cu-A-cytochrome c domain grafted to this membrane anchor can facilitate electron transfer from reduced TMPD to low-spin protoheme b in subunit I.

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  • Identification and characterization of 9-cis-hexadecenoic acid cis-trans isomerase of Pseudomonas sp. strain E-3 Reviewed

    H Okuyama, D Enari, T Kusano, N Morita

    PHYSIOLOGY, BIOCHEMISTRY AND MOLECULAR BIOLOGY OF PLANT LIPIDS   84 - 86   1997

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    Language：English   Publishing type：Research paper (international conference proceedings)   Publisher：KLUWER ACADEMIC PUBL  

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  • Nucleotide and amino acid sequences for cytochrome caa(3)-type oxidase of Bacillus stearothermophilus K1041 and non-Michaelis-type kinetics with cytochrome c Reviewed

    T Kusano, S Kuge, J Sakamoto, S Noguchi, N Sone

    BIOCHIMICA ET BIOPHYSICA ACTA-BIOENERGETICS   1273 ( 2 )   129 - 138   1996.2

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    Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER SCIENCE BV  

    A pseudo-sigmoidal cytochrome c-dependence curve of oxidase activity was observed with cytochrome oxidase from the Bacillus stearothermophilus strain K1041, while the other thermophilic Bacillus PS3 which has been extensively studied possessed normal Michaelis-Menten type kinetics. The genes coding for four subunits of cytochrome caa(3)-type oxidase and for heme O synthase were isolated from a genomic DNA library of K1041 by using a PS3 DNA fragment containing the highly-conserved region of the largest subunit as a probe, and sequenced. Most residues in subunits I (COI/caaB product), III (COIII/caaC product), and IV (COIV/caaD product) of K1041 were highly conserved when compared with those of PS3. However, the sequence of K1041 subunit II (COII/caaA product) was distinctly different from that of the PS3 subunit II. These Bacillus COIIs have an additional sequence for cytochrome c after the Cu-A binding protein portion with two transmembrane segments which is homologous to the mitochondrial counterpart, and represents the site of electron ingress. Several charged residues in the vicinity of cytochrome c moiety are replaced by oppositely charged residues. It is likely that these amino acid replacements in subunit II are the cause of the abnormal sigmoidal saturation curve for extrinsic cytochromes c of the K1041 enzyme.

    DOI： 10.1016/0005-2728(95)00126-3

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Misc.

  • キサンチン脱水素酵素/酸化酵素変換におけるラクトペルオキシダーゼの生理作用

    草野輝男, 岡本研

    日本生化学会大会(Web)   92nd   2019

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  • 低酸素環境下でのマウス脳内プリン代謝へのキサンチン酸化還元酵素阻害剤の影響

    草野輝男, 岡本研

    日本痛風・核酸代謝学会総会プログラム・抄録集   52nd   2019

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  • Allopurinolとその誘導体がプリン代謝に与える影響の解析

    関根舞, 草野輝男, 西野武士, 岡本研

    日本痛風・核酸代謝学会総会プログラム・抄録集   52nd   2019

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  • マウス神経細胞において活性酸素種の役割：XOR変異マウスとプリン誘導体のメタボローム解析

    草野 輝男, 岡本 研

    痛風と核酸代謝   42 ( 1 )   116 - 116   2018.7

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    Language：Japanese   Publisher：一般社団法人 日本痛風・核酸代謝学会  

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  • プリンサルベージ酵素の種差と酵素学的性質の解析

    関根舞, 草野輝男, 永田宏次, 西野武士, 岡本研

    日本生化学会大会(Web)   91st   2018

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  • 低酸素環境下でのマウス脳内プリン代謝の変動

    草野輝男, 岡本研

    日本生化学会大会(Web)   91st   2018

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  • ウサギ網状赤血球のプリン代謝調節

    関根舞, 草野輝男, 永田宏次, 西野武士, 西野武士, 岡本研

    日本生化学会大会(Web)   90th   ROMBUNNO.2LBA‐002 (WEB ONLY)   2017

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  • 全脳虚血再灌流障害モデルマウスにおける酸化ストレスマーカーの検討

    山口 昌紘, 鈴木 剛, 草野 輝男, 布施 明, 岡本 研, 折茂 英生, 横田 裕行

    日本救急医学会雑誌   25 ( 8 )   472 - 472   2014.8

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    Language：Japanese   Publisher：(一社)日本救急医学会  

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  • 病態に根ざしたALSの新規治療法開発 非プリン型キサンチン酸化還元酵素(XOR)阻害剤による筋萎縮性側索硬化症(ALS)細胞死抑制効果の臨床病理学的解析

    加藤信介, 加藤雅子, 瀧川みき, 草野輝男, 西野武士

    神経変性疾患に関する調査研究班 分科班「病態に根ざしたALSの新規治療法開発」 平成25年度 研究報告書   49 - 53   2014

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  • 病態に根ざしたALSの新規治療法開発 プリンサルベージ回路の基質とならないキサンチン酸化還元酵素(XOR)阻害剤による筋萎縮性側索硬化症治療薬(ALS)の可能性

    加藤信介, 加藤雅子, 草野輝男, 西野武士

    神経変性疾患に関する調査研究班分科班「病態に根ざしたALSの新規治療法開発」 平成24年度 研究報告書   49 - 53   2013

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  • キサンチン酸化還元阻害薬と3vessel occlusion modelを用いたマウスの脳虚血再還流障害の解析

    鈴木剛, 布施明, 横田裕行, 松村智裕, 岡本研, 草野輝男, 内藤善哉, 石渡俊行, 松田陽子, 西野武士

    日本救急医学会雑誌   23 ( 10 )   521 - 521   2012.10

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  • 3 vessel occlusion modelを用いたマウスの脳虚血再還流障害の解析

    鈴木剛, 布施明, 横田裕行, 松村智裕, 岡本研, 草野輝男, 内藤善哉, 石渡俊行, 松田陽子, 西野武士

    Shock   27 ( 1 )   75 - 75   2012.4

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    Language：Japanese   Publisher：(一社)日本Shock学会  

    J-GLOBAL

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  • キサンチン酸化還元酵素変異トランスジェニックマウスの作成と3-vessel occlusion modelを用いたマウスの脳虚血性再灌流障害の解析

    鈴木 剛, 布施 明, 松本 学, 金 史英, 辻井 厚子, 横田 裕行, 村松 智裕, 草野 輝男, 内藤 善哉, 松田 陽子, 西野 武士

    日本救急医学会雑誌   22 ( 8 )   586 - 586   2011.8

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    Language：Japanese   Publisher：(一社)日本救急医学会  

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  • ウシキサンチン酸化還元酵素と天然基質キサンチンとの反応中間体結晶構造

    岡本研, 草野輝男, 松村智裕, 松本浩二, 西野武士, 西野武士

    生化学   2010

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  • Knock-outマウスを用いたラクトペルオキシダーゼの組織局在の網羅的解析

    草野 輝男, 松田 陽子, 西野 朋子, 石渡 俊行, 内藤 善哉, 西野 武士

    日本生化学会大会プログラム・講演要旨集   82回   2P - 595   2009.9

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    Language：Japanese   Publisher：(公社)日本生化学会  

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  • キサンチン酸化還元酵素の基質結合様式と基質活性化機構

    岡本研, 松村智裕, 草野輝男, 松本浩二, 西野武士

    生化学   2009

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  • ブチロフィリンが有す多機能B30.2/SPRYドメインとミルクキサンチン酸化還元酵素との結合様式について

    西野朋子, LI Ying, 岡本研, 草野輝男, 川口裕子, 松村智裕, 青木直人, 松田幹, 西野武士

    生化学   2009

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  • ヒト3-phosphoglycerate kinaseの結晶構造と欠損症患者変異酵素を用いたドメイン開閉機構の解析

    赤塚早紀, 草野輝男, 松村智裕, 岡本研, 西野武士

    生化学   2008

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  • キサンチン脱水素酵素-酸化酵素変換の役割

    LI Ying, 西野朋子, 岡本研, 川口裕子, 草野輝男, 松村智裕, 青木直人, 松田幹, 西野武士

    生化学   2007

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  • C-43 低温微生物Pseudomonas sp. E-3株の分類学的検討(極限環境,C会場,ポスター発表)

    湯本 勲, 草野 輝男, 信行 友寛, 野田坂 佳伸, 松山 英俊, 奥山 英登志

    日本微生物生態学会講演要旨集   ( 17 )   125 - 125   2001

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    Language：Japanese   Publisher：日本微生物生態学会  

    CiNii Books

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Presentations

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Research Projects

  • Structure-function studies of bacterial mitoNEET system

    Grant number：26670215  2014.4 - 2016.3

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Challenging Exploratory Research

    Iwasaki Toshio, KUSANO TERUO, KUMASAKA TAKASHI, IWASAKI HIDEO

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    Grant amount：\3510000 （ Direct Cost: \2700000 、 Indirect Cost：\810000 ）

    MitoNEET is a novel outer-mitochondrial membrane iron-sulfur protein, recently identified as a potential mitochondrial target that binds pioglitazone, an insulin sensitizer for the treatment of type II diabetes. Recently we constructed a null-deletion mutant strain of Thermus thermophilus lacking TthNEET (the thermophile homolog of mitoNEET), and found a “prokaryotic glucose intolerance” for this delta-TthNEET null strain. In this work, we characterized TthNEET mutant proteins and strains with altered [2Fe-2S] cluster redox potentials by X-ray crystallographic and physiological analyses to better understand the structure-function relationships of this class of proteins, and explored the protein interaction network of TthNEET by monitoring the whole-cell global changes of the Thermus protein components, using pulldown assays and two-dimensional gel electrophoresis.

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  • Systemic and long term analysys of O2- hyperproduction mice

    Grant number：24590393  2012.4 - 2015.3

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (C)

    OKAMOTO Ken, KUSANO Teruo

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    Grant amount：\5330000 （ Direct Cost: \4100000 、 Indirect Cost：\1230000 ）

    Xanthine oxidoreductase (XOR) inhibitors are reported to protect tissues from damage caused by reactive oxygen species (ROS) by inhibiting its production through XOR inhibition. We analyzed the effects of inhibitors in decreasing global severe cerebral I/R damage in mice. Mice were divided into three groups: a placebo group, an allopurinol group, and a febuxostat group. Each groups was performed pathological examination on the CA1 and CA2 regions of the hippocampus 4 days after I/R surgery, which revealed that the number of neuronal cells decreased in the 14-min occlusion model in both regions but the drugs administered to prevent this damage were not effective. One of the reasons for the less effectiveness of XOR inhibitors to control severe whole brain ischemia in mouse model is due to the low levels of expression of XOR in the mouse brain.
    We analyzed molecular mechanism of ROS production by XOR using C-terminal deleted mutant, and published the result as an original article.

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  • Structure-function of bacterial mitoNEET homologs

    Grant number：24659202  2012.4 - 2014.3

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Challenging Exploratory Research

    IWASAKI TOSHIO, KUSANO Teruo, KUMASAKA Takashi, IWASAKI Hideo

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    Grant amount：\3640000 （ Direct Cost: \2800000 、 Indirect Cost：\840000 ）

    MitoNEET is a mammalian mitochondrial outer membrane iron-sulfur protein with a potential pharmacological and clinical target of pioglitazone, an insulin-sensitizer for the treatment of type II diabetes. In this study, we conducted the phenotypal analyses of a deletion strain and several mutant strains of a bacterial mitoNEET homolog (TthNEET) of Thermus thermophilus HB8 in comparison with the wild-type strain, and re-analyzed the available metabolome and microarray datasets of this thermophile. We also obtained the high-resolution X-ray diffraction datasets of mammalian mitoNEET in complex with several drug compounds.

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  • Effects of Change in Purine Metabolism on Accumulation of Aggregated Proteins in the Cell

    Grant number：24659144  2012

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Challenging Exploratory Research

    NISHINO Takeshi, KUSANO Teruo, MIYAGAWA Takuya

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    Grant amount：\3900000 （ Direct Cost: \3000000 、 Indirect Cost：\900000 ）

    We orally administered recently introduced potent xanthine oxidoreductase inhibitors, whose mechanisms of inhibition are well characterized, to ALS G1H-G93A mice. The results of modelexperiments indicated that orally administered non-purine analogue XOR inhibitors significantly delaythe disease progression. The protective effect is suggested to be due to increased removal ofaggregated protein accompany with change in purine metabolism by the experiment with modelsystems.

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  • Phasogenesis study of XOR mutant knock-in mouse.

    Grant number：20590317  2008 - 2010

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (C)

    OKAMOTO Ken, MATSUMURA Tomohiro, KUSANO Teruo

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    Grant amount：\4810000 （ Direct Cost: \3700000 、 Indirect Cost：\1110000 ）

    We designed and constructed O2- hyperproduction XOR mutant knoched-in mouse which and dehydrogenase-type locked mutant knoched-in mouse. We propagated the starins. We purified mutant XOR from the knocked-in mutant mouse liver and confirmed the hyper production of superoxide anion. We are observing the phenotypes of the mutans and surveying pathological findings of organs.

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Teaching Experience

  • 食品物理化学

    2023.4
    Institution：東京大学大学院

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  • 代謝栄養学

    2020
    Institution：日本医科大学看護専門学校

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  • 基礎医学総論

    2019
    Institution：日本医科大学

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  • 生化学

    2015
    Institution：日本医科大学

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