Updated on 2022/06/14

写真a

 
TSUJI Tokuji
 
Organization
Graduate School of Pharmaceutical Sciences Department of Basic Medicinal Sciences Bioscience Assistant Professor
Graduate School
Graduate School of Pharmaceutical Sciences
Title
Assistant Professor

Degree 1

  1. Ph.D. (lifescience) ( 2017.3   Kyoto University ) 

Research Interests 4

  1. 表皮分化

  2. Zinc

  3. Phospholipid

  4. Transporter

Research Areas 3

  1. Life Science / Applied molecular and cellular biology

  2. Life Science / Cell biology

  3. Life Science / Molecular biology

Research History 5

  1. Nagoya University   Graduare School of Pharmaceutical Sciences   Assistant Professor

    2021.10

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    Country:Japan

  2. Kyoto University   Graduate School of Biostudies   Program-Specific Researcher

    2020.6 - 2021.9

  3. Shiga University of Medical Science   University Hospital   Designated assistant professor

    2019.4 - 2020.5

  4. Shiga University of Medical Science   University Hospital

    2017.4 - 2019.3

  5. Japan Society for Promotion of Science

    2015.4 - 2017.3

Education 3

  1. Kyoto University

    2013.4 - 2017.3

  2. Kyoto University

    2011.4 - 2013.3

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    Country: Japan

  3. Kyoto University

    2007.4 - 2011.3

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    Country: Japan

Professional Memberships 4

  1. THE PHARMACEUTICAL SOCIETY OF JAPAN

  2. JAPAN SOCIETY FOR BIOSCIENCE, BIOTECHNOLOGY, AND AGROCHEMISTRY

  3. THE MEMBRANE SOCIETY OF JAPAN

  4. THE JAPANESE CONFERENCE ON THE BIOCHEMISTRY OF LIPIDS

Awards 3

  1. 第34回滋賀医大シンポジウム 審査員特別賞

    2017.12   滋賀医科大学  

    辻 徳治

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    Award type:Award from Japanese society, conference, symposium, etc. 

  2. 第11回次世代を担う若手医療薬科学シンポジウム 優秀発表賞

    2017.10   日本薬学会医療薬科学部会  

    辻 徳治

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    Award type:Award from Japanese society, conference, symposium, etc. 

  3. メタルバイオサイエンス研究会2015 若手優秀賞

    2015.8   日本毒性学会 生体金属部会  

    辻 徳治

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    Award type:Award from Japanese society, conference, symposium, etc. 

 

Papers 9

  1. Application of enzymatic fluorometric assays to quantify phosphatidylcholine, phosphatidylethanolamine and sphingomyelin in human plasma lipoproteins Reviewed

    Tokuji Tsuji, Tatsushi Yuri, Tomohiro Terada, Shin-Ya Morita

    Chemistry and Physics of Lipids   Vol. 238   page: 105102 - 105102   2021.6

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

    DOI: 10.1016/j.chemphyslip.2021.105102

    PubMed

  2. Alterations in cellular and organellar phospholipid compositions of HepG2 cells during cell growth Reviewed International journal

    Tokuji Tsuji, Shin-ya Morita, Yoshinobu Nakamura, Yoshito Ikeda, Taiho Kambe, Tomohiro Terada

    Scientific Reports   Vol. 11 ( 1 ) page: 2731   2021.2

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    Authorship:Lead author   Language:English   Publishing type:Research paper (scientific journal)   Publisher:Springer Science and Business Media LLC  

    <title>Abstract</title>The human hepatoblastoma cell line, HepG2, has been used for investigating a wide variety of physiological and pathophysiological processes. However, less information is available about the phospholipid metabolism in HepG2 cells. In the present report, to clarify the relationship between cell growth and phospholipid metabolism in HepG2 cells, we examined the phospholipid class compositions of the cells and their intracellular organelles by using enzymatic fluorometric methods. In HepG2 cells, the ratios of all phospholipid classes, but not the ratio of cholesterol, markedly changed with cell growth. Of note, depending on cell growth, the phosphatidic acid (PA) ratio increased and phosphatidylcholine (PC) ratio decreased in the nuclear membranes, the sphingomyelin (SM) ratio increased in the microsomal membranes, and the phosphatidylethanolamine (PE) ratio increased and the phosphatidylserine (PS) ratio decreased in the mitochondrial membranes. Moreover, the mRNA expression levels of enzymes related to PC, PE, PS, PA, SM and cardiolipin syntheses changed during cell growth. We suggest that the phospholipid class compositions of organellar membranes are tightly regulated by cell growth. These findings provide a basis for future investigations of cancer cell growth and lipid metabolism.

    DOI: 10.1038/s41598-021-81733-3

    PubMed

    Other Link: http://www.nature.com/articles/s41598-021-81733-3

  3. Enzymatic fluorometric assays for quantifying all major phospholipid classes in cells and intracellular organelles Reviewed

    Tokuji Tsuji, Shin-ya Morita, Yoshito Ikeda, Tomohiro Terada

    Scientific Reports   Vol. 9 ( 1 ) page: 8607   2019.12

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    Authorship:Lead author   Language:English   Publishing type:Research paper (scientific journal)   Publisher:Springer Science and Business Media LLC  

    DOI: 10.1038/s41598-019-45185-0

    Other Link: http://www.nature.com/articles/s41598-019-45185-0

  4. Dissecting the Process of Activation of Cancer-promoting Zinc-requiring Ectoenzymes by Zinc Metalation Mediated by ZNT Transporters Reviewed

    Tokuji Tsuji, Yayoi Kurokawa, Johanna Chiche, Jacques Pouyssegur, Hiroshi Sato, Hideya Fukuzawa, Masaya Nagao, Taiho Kambe

    JOURNAL OF BIOLOGICAL CHEMISTRY   Vol. 292 ( 6 ) page: 2159 - 2173   2017.2

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    Authorship:Lead author   Language:English   Publishing type:Research paper (scientific journal)   Publisher:AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC  

    Zinc-requiring ectoenzymes, including both secreted and membrane-bound enzymes, are considered to capture zinc in their active site for their activation in the early secretory pathway. This idea has been confirmed by our studies conducted using tissue-nonspecific alkaline phosphatase (TNAP), which is elaborately activated by means of a two-step mechanism by zinc transporter 5 (ZNT5)-ZNT6 heterodimers and ZNT7 homodimers, through protein stabilization followed by enzyme activation with zinc in the early secretory pathway. However, the molecular basis of the activation process in other zinc-requiring ectoenzymes remains largely unknown. In this study, we investigated this activation process by using three cancer- promoting zinc-requiring ectoenzymes, autotaxin (ATX), matrix metalloproteinase 9 (MMP9), and carbonic anhydrase IX (CAIX), and the chicken DT40 cell mutants that we generated; we specifically focused on clarifying whether the same or a similar activation mechanism operates in these ectoenzymes. ATX activation required ZNT5-ZNT6 heterodimers and ZNT7 homodimers in a manner similar to TNAP activation, although the protein stability of ATX was differently regulated from that of TNAP. MMP9 required ZNT5-ZNT6 heterodimers and ZNT7 homodimers for its activation as well as secretion; MMP9 was not secreted into the spent medium unless both zinc-transport complexes were present. Finally, CAIX activation by zinc was mediated not only by ZNT5-ZNT6 heterodimers and ZNT7 homodimers but also by ZNT4 homodimers; thus, these three zinc-transport complexes redundantly contribute to CAIX activation. Our results provide pivotal insights into the activation processes of zinc-requiring ectoenzymes, and furthermore, they offer novel insights for potential cancer therapy applications given the cancer-promoting potencies of ATX, MMP9, and CAIX.

    DOI: 10.1074/jbc.M116.763946

    Web of Science

  5. Early secretory pathway-resident Zn transporter proteins contribute to cellular sphingolipid metabolism through activation of sphingomyelin phosphodiesterase 1 Reviewed

    Sachiko Ueda, Yuki Manabe, Naoya Kubo, Naho Morino, Hana Yuasa, Miku Shiotsu, Tokuji Tsuji, Tatsuya Sugawara, Taiho Kambe

    American Journal of Physiology-Cell Physiology   Vol. 322 ( 5 ) page: C948 - C959   2022.3

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

  6. Detailed analyses of the crucial functions of Zn transporter proteins in alkaline phosphatase activation. Reviewed International journal

    Eisuke Suzuki, Namino Ogawa, Taka-Aki Takeda, Yukina Nishito, Yu-Ki Tanaka, Takashi Fujiwara, Mayu Matsunaga, Sachiko Ueda, Naoya Kubo, Tokuji Tsuji, Ayako Fukunaka, Tomohiro Yamazaki, Kathryn M Taylor, Yasumitsu Ogra, Taiho Kambe

    The Journal of biological chemistry   Vol. 295 ( 17 ) page: 5669 - 5684   2020.4

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

    Numerous zinc ectoenzymes are metalated by zinc and activated in the compartments of the early secretory pathway before reaching their destination. Zn transporter (ZNT) proteins located in these compartments are essential for ectoenzyme activation. We have previously reported that ZNT proteins, specifically ZNT5-ZNT6 heterodimers and ZNT7 homodimers, play critical roles in the activation of zinc ectoenzymes, such as alkaline phosphatases (ALPs), by mobilizing cytosolic zinc into these compartments. However, this process remains incompletely understood. Here, using genetically-engineered chicken DT40 cells, we first determined that Zrt/Irt-like protein (ZIP) transporters that are localized to the compartments of the early secretory pathway play only a minor role in the ALP activation process. These transporters included ZIP7, ZIP9, and ZIP13, performing pivotal functions in maintaining cellular homeostasis by effluxing zinc out of the compartments. Next, using purified ALP proteins, we showed that zinc metalation on ALP produced in DT40 cells lacking ZNT5-ZNT6 heterodimers and ZNT7 homodimers is impaired. Finally, by genetically disrupting both ZNT5 and ZNT7 in human HAP1 cells, we directly demonstrated that the tissue-nonspecific ALP-activating functions of both ZNT complexes are conserved in human cells. Furthermore, using mutant HAP1 cells, we uncovered a previously-unrecognized and unique spatial regulation of ZNT5-ZNT6 heterodimer formation, wherein ZNT5 recruits ZNT6 to the Golgi apparatus to form the heterodimeric complex. These findings fill in major gaps in our understanding of the molecular mechanisms underlying zinc ectoenzyme activation in the compartments of the early secretory pathway.

    DOI: 10.1074/jbc.RA120.012610

    PubMed

  7. Protocols for Enzymatic Fluorometric Assays to Quantify Phospholipid Classes Invited Reviewed

    Shin-ya Morita, Tokuji Tsuji, Tomohiro Terada

    Int. J. Mol. Sci.   Vol. 21 ( 3 ) page: 1032   2020.2

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

  8. Enhancing effect of taurohyodeoxycholate on ABCB4-mediated phospholipid efflux. Reviewed

    Yoshito Ikeda, Shin-ya Morita, Ryo Hatano, Tokuji Tsuji, Tomohiro Terada

    BBA-Mol. Cell Biol. Lipids   Vol. 1864 ( 10 ) page: 1495 - 502   2019.6

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

  9. Molecular Mechanisms for Protection of Hepatocytes against Bile Salt Cytotoxicity Invited Reviewed

    Shin-ya Morita, Yoshito Ikeda, Tokuji Tsuji, Tomohiro Terada

    Chem. Pharm. Bull.   Vol. 67 ( 4 ) page: 333 - 340   2019

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

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MISC 2

  1. 亜鉛の生体機能と亜鉛の細胞輸送機構

    神戸大朋, 辻徳治

    金属   Vol. 91 ( 9 ) page: 752 - 758   2021.8

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    Language:Japanese   Publishing type:Article, review, commentary, editorial, etc. (scientific journal)  

  2. Development of enzymatic fluorometric methods for measuring all major phospholipid classes and search for disease biomarkers Invited

    Tokuji Tsuji

      Vol. 37   page: 91 - 97   2021.3

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    Authorship:Lead author, Corresponding author   Language:Japanese   Publishing type:Article, review, commentary, editorial, etc. (other)  

Presentations 12

  1. Quantitative analysis of major phospholipid classes in cells and organelles by novel enzymatic fluometric methods International conference

    Tokuji Tsuji, Shin-ya Morita, Yoshito Ikeda, Tomohiro Terada

    60th International Conference on the Bioscience of Lipids  2019.6.18 

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    Language:English   Presentation type:Poster presentation  

  2. ホスファチジルイノシトールに対する新規定量法の開発と細胞内全リン脂質クラスの定量的解析

    辻 徳治

    2017年度第8回学際的脂質創生研究部会講演会  2018.1.26 

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    Language:Japanese   Presentation type:Oral presentation (general)  

  3. Quantitative analysis of major phospholipid classes in organelle membranes by enzymatic fluometric assay.

    Tokuji TSUJI

    2019.5.9 

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    Language:Japanese   Presentation type:Oral presentation (general)  

  4. 酵素蛍光定量法を用いた細胞小器官における主要リン脂質組成の分析

    辻徳治, 森田真也, 池田義人, 寺田智祐

    第60回日本脂質生化学会  2018.5.31 

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    Language:Japanese   Presentation type:Oral presentation (general)  

  5. 酵素蛍光定量法を用いた細胞小器官における主要リン脂質クラスの定量分析

    辻徳治

    第40回生体膜と薬物の相互作用シンポジウム  2018.10.19 

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    Language:Japanese   Presentation type:Oral presentation (general)  

  6. 酵素蛍光定量法を用いた細胞増殖に伴う細胞内リン脂質組成変化の定量分析

    辻徳治, 森田真也, 中村吉伸, 寺田智祐

    第62回日本脂質生化学会  2020.5.14 

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    Presentation type:Oral presentation (general)  

  7. 全主要リン脂質クラスを網羅的に解析する酵素蛍光定量法の開発

    辻 徳治, 森田真也, 池田義人, 寺田智祐

    第11回次世代を担う若手医療薬科学シンポジウム  2017.10.21 

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    Language:Japanese   Presentation type:Poster presentation  

  8. 全主要リン脂質クラスを網羅的に解析する酵素蛍光定量法の開発 Invited

    辻 徳治, 森田真也, 池田義人, 寺田智祐

    医療薬学フォーラム2018  2018.7.9 

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    Language:Japanese   Presentation type:Symposium, workshop panel (nominated)  

  9. 主要リン脂質クラスを網羅的に定量する酵素蛍光定量法の開発

    辻 徳治, 森田真也, 池田義人, 寺田智祐

    第34回滋賀医大シンポジウム  2017.12.15 

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    Language:Japanese   Presentation type:Oral presentation (general)  

  10. ホスファチジルイノシトール酵素蛍光定量法の開発と細胞内全リン脂質クラス組成に関する定量的解析

    辻 徳治, 森田真也, 池田義人, 寺田智祐

    第39回生体膜と薬物の相互作用シンポジウム  2017.10.27 

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    Language:Japanese   Presentation type:Oral presentation (general)  

  11. ホスファチジルイノシトール定量法の新規開発と細胞内主要リン脂質クラスの定量的解析

    辻 徳治, 森田真也, 池田義人, 寺田智祐

    日本農芸化学会2018年度大会  2018.3.17 

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    Language:Japanese   Presentation type:Oral presentation (general)  

  12. ホスファチジルイノシトールに対する酵素蛍光定量法の開発と細胞内リン脂質クラスの網羅的定量

    辻 徳治, 森田真也, 池田義人, 寺田智祐

    日本薬学会第138年会  2018.3.27 

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    Language:Japanese   Presentation type:Oral presentation (general)  

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Research Project for Joint Research, Competitive Funding, etc. 3

  1. 酵素蛍光法を用いた主要リン脂質クラスの網羅的定量法の開発と疾患バイオマーカーの探索 International coauthorship

    2018.4 - 2020.3

    平成29年度薬学研究奨励財団研究助成金 

    辻 徳治

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    Authorship:Principal investigator 

  2. 新規リン脂質定量分析法を用いた腸上皮細胞のリン脂質代謝機構に関する研究

    2018.4 - 2019.3

    平成30年度滋賀医科大学学長裁量経費 (若手萌芽研究)  新規リン脂質定量分析法を用いた腸上皮細胞のリン脂質代謝機構に関する研究

    辻 徳治

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    Authorship:Principal investigator  Grant type:Competitive

  3. 主要リン脂質クラスを網羅的に定量する酵素蛍光定量法の開発

    2018.4 - 2019.3

    第34回滋賀医大シンポジウムによる研究助成金 

    辻 徳治

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    Grant type:Competitive

KAKENHI (Grants-in-Aid for Scientific Research) 2

  1. Exploration of a suppressor of atherosclerotic coronary artery disease by using a novel method for measurement of phospholipids

    Grant number:19K23799  2019.10 - 2021.3

    Japan Society for the Promotion of Science  Grant-in-Aid for Research Activity start-up 

    Tokuji TSUJI

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    Authorship:Principal investigator  Grant type:Competitive

    Grant amount:\2860000 ( Direct Cost: \2200000 、 Indirect Cost:\660000 )

  2. がん関連酵素の活性化に関わる亜鉛トランスポーターに着目したがん抑制に関する研究

    Grant number:15J08286  2015.4 - 2017.3

    日本学術振興会  科学研究費補助金 (特別研究員奨励費) 

    辻 徳治

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    Authorship:Principal investigator  Grant type:Competitive

    Grant amount:\170000 ( Direct Cost: \170000 )