Updated on 2024/03/09

写真a

 
NAKASHIMA Fumie
 
Organization
Graduate School of Bioagricultural Sciences Department of Applied Biosciences Assistant Professor
Graduate School
Graduate School of Bioagricultural Sciences
Undergraduate School
School of Agricultural Sciences Department of Applied Biosciences
Title
Assistant Professor
External link

Degree 1

  1. Ph.D. (Agriculture) ( 2018.3   Nagoya University ) 

Research Areas 2

  1. Life Science / Food sciences

  2. Life Science / Pharmacology  / bioactive lipids

Current Research Project and SDGs 2

  1. 食品の機能性に関する研究

  2. 新規生理活性脂質の探索およびその生理活性解明

Research History 4

  1. Nagoya University   Graduate School of Bioagricultural Sciences   Assistant Professor

    2022.2

      More details

    Country:Japan

    researchmap

  2. Vanderbilt University Medical School   Postdoctoral Fellow

    2018.11 - 2022.1

      More details

    Country:United States

    researchmap

  3. Nagoya University   Graduat   Researcher

    2018.3 - 2018.11

      More details

    Country:Japan

  4. Japan Society for Promotion of Science   Researcher

    2016.4 - 2018.3

      More details

    Country:Japan

Education 3

  1. Nagoya University   Graduate School of Bioagricultural Sciences   Department of Applied Biosciences

    2015.4 - 2018.3

      More details

    Country: Japan

  2. Nagoya University   Graduate School of Bioagricultural Sciences   Department of Applied Biosciences

    2013.4 - 2015.3

      More details

    Country: Japan

  3. Nagoya University   School of Agricultural Sciences   Department of Applied Biosciences

    2009.4 - 2013.3

      More details

    Country: Japan

Professional Memberships 2

  1. 日本生化学会

    2014.9

  2. 日本農芸化学会

    2013

      More details

Awards 1

  1. 名古屋大学学術奨励賞受賞

    2017.6   名古屋大学  

 

Papers 18

  1. The 5-lipoxygenase/cyclooxygenase-2 cross-over metabolite, hemiketal E2, enhances VEGFR2 activation and promotes angiogenesis. Reviewed International coauthorship International journal

    Fumie Nakashima, Juan A Giménez-Bastida, Paula B Luis, Sai H Presley, Robert E Boer, Manuel Chiusa, Takahiro Shibata, Gary A Sulikowski, Ambra Pozzi, Claus Schneider

    The Journal of biological chemistry   Vol. 299 ( 4 ) page: 103050 - 103050   2023.4

     More details

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

    Consecutive oxygenation of arachidonic acid by 5-lipoxygenase and cyclooxygenase-2 yields the hemiketal eicosanoids, HKE2 and HKD2. Hemiketals stimulate angiogenesis by inducing endothelial cell tubulogenesis in culture; however, how this process is regulated has not been determined. Here, we identify vascular endothelial growth factor receptor 2 (VEGFR2) as a mediator of HKE2-induced angiogenesis in vitro and in vivo. We found that HKE2 treatment of human umbilical vein endothelial cells dose-dependently increased the phosphorylation of VEGFR2 and the downstream kinases ERK and Akt that mediated endothelial cell tubulogenesis. In vivo, HKE2 induced the growth of blood vessels into polyacetal sponges implanted in mice. HKE2-mediated effects in vitro and in vivo were blocked by the VEGFR2 inhibitor vatalanib, indicating that the pro-angiogenic effect of HKE2 was mediated by VEGFR2. HKE2 covalently bound and inhibited PTP1B, a protein tyrosine phosphatase that dephosphorylates VEGFR2, thereby providing a possible molecular mechanism for how HKE2 induced pro-angiogenic signaling. In summary, our studies indicate that biosynthetic cross-over of the 5-lipoxygenase and cyclooxygenase-2 pathways gives rise to a potent lipid autacoid that regulates endothelial cell function in vitro and in vivo. These findings suggest that common drugs targeting the arachidonic acid pathway could prove useful in antiangiogenic therapy.

    DOI: 10.1016/j.jbc.2023.103050

    Web of Science

    Scopus

    PubMed

    researchmap

  2. Biosynthetic Crossover of 5-Lipoxygenase and Cyclooxygenase-2 Yields 5-Hydroxy-PGE2 and 5-Hydroxy-PGD2 Reviewed International coauthorship

    Fumie Nakashima, Takashi Suzuki, Odaine N. Gordon, Dominic Golding, Toshiaki Okuno, Juan A. Giménez-Bastida, Takehiko Yokomizo, Claus Schneider

    JACS Au   Vol. 1 ( 9 ) page: 1380 - 1388   2021.8

     More details

    Authorship:Lead author   Language:English   Publishing type:Research paper (scientific journal)   Publisher:American Chemical Society (ACS)  

    DOI: 10.1021/jacsau.1c00177

    PubMed

    researchmap

  3. Eriodictyol and thymonin act as GPR35 agonists. Reviewed International journal

    Fumie Nakashima, Wei Qi Loh, Mayuka Wakabayashi, Sayako Shimomura, Hiroyuki Hattori, Masaki Kita, Asuka Inoue, Koji Uchida, Takahiro Shibata

    Bioscience, biotechnology, and biochemistry   Vol. 87 ( 12 ) page: 1514 - 1522   2023.11

     More details

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

    Although herbs and spices have been used in traditional medicine for more than a century owing to their health benefits, the associated underlying mechanism is still not clear. Since the G protein-coupled receptor 35 (GPR35) has been linked to exert various antioxidant and anti-inflammatory effects, we screened 19 different herbs and spices for possible GPR35 agonist(s) to understand the GPR35-dependent functions on herbs and spices. Among the screened extracts, the ethyl acetate extract of thyme exhibited a remarkable GPR35 agonistic activity. Activity-guided separations allowed us to identify two polyphenolic phytochemicals, eriodictyol and thymonin, acting as GPR35 agonists. Both eriodictyol and thymonin showed a potent and specific agonist activity toward GPR35 with half maximal effective concentration values of 5.48 and 8.41 μM, respectively. These findings indicate that these phytochemicals may have beneficial health effects upon GPR35 activation.

    DOI: 10.1093/bbb/zbad125

    Web of Science

    Scopus

    PubMed

    researchmap

  4. Sodium sulfite causes gastric mucosal cell death by inducing oxidative stress Reviewed

    Oshimo M, Nakashima F, Kai K, Matsui H, Shibata T, Akagawa M

    Free Radical Research   Vol. 55 ( 6 ) page: 731 - 743   2021.6

     More details

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

    Sulfites are commonly used as a preservative and antioxidant additives in the food industry. Sulfites are absorbed by the gastrointestinal tract and distributed essentially to all body tissues. Although sulfites have been believed to be safe food additives, some studies have shown that they exhibit adverse effects in various tissues. In this study, we examined the cytotoxic effect of sodium sulfite (Na2SO3) against rat gastric mucosal cells (RGM1) and further investigated its underlying molecular mechanism. We demonstrated that exposure to Na2SO3 exerts significant cytotoxicity in RGM1 cells through induction of oxidative stress. Exposure of RGM1 cells to Na2SO3 caused a significant formation of protein carbonyls and 8-hydroxy-2'-deoxyguanosine, major oxidative stress markers, with a concomitant accumulation of carbonylated protein-related aggregates. Furthermore, we found that incubation of lysozyme with Na2SO3 evokes protein carbonylation and aggregation via the metal ion-catalyzed free radical formation derived from Na2SO3. Our results suggest that Na2SO3 might lead to gastric tissue injury via induction of oxidative stress by the formation of Na2SO3-related free radicals.

    DOI: 10.1080/10715762.2021.1937620

    Web of Science

    Scopus

    PubMed

    researchmap

  5. Mechanistic Differences in the Inhibition of NF-κB by Turmeric and Its Curcuminoid Constituents Reviewed International coauthorship

    Edwards RL, Luis PB, Nakashima F, Kunihiro AG, Presley SH, Funk JL, Schneider C

      Vol. 68   page: 6154 - 6160   2020.5

     More details

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

    DOI: 10.1021/acs.jafc.0c02607

  6. Transformation of Prostaglandin D2 to 11-Dehydro Thromboxane B2 by Baeyer-Villiger Oxidation Reviewed International coauthorship

    Nakashima F, Schneider C

    Lipids   Vol. 55   page: 73 - 78   2019.12

     More details

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

  7. A unique mechanism for thiolation of serum albumins by disulphide molecules Invited Reviewed

    Nakashima F, Shibata T, Uchida K

    The Journal of Biochemistry   Vol. 167 ( 2 ) page: 165 - 171   2019.10

     More details

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

    DOI: 10.1093/jb/mvz084

  8. Curcumin induces secretion of glucagon-like peptide-1 through an oxidation-dependent mechanism Reviewed International coauthorship

    Alli-Oluwafuyi AM, Luis PB, Nakashima F, Giménez-Bastida JA, Presley SH, Duvernay MT, Iwalewa EO, Schneider C

    Biochimie   Vol. 165   page: 250 - 257   2019.8

     More details

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

    DOI: https://doi.org/10.1016/j.biochi.2019.08.013

  9. A Dual Perspective of the Action of Lysine on Soybean Oil Oxidation Process Obtained by Combining 1H NMR and LC-MS: Antioxidant Effect and Generation of Lysine-Aldehyde Adducts Reviewed International coauthorship

    Martin-Rubio AS, Sopelana P, Nakashima F, Shibata T, Uchida K, Guillén MD

    Antioxidants   Vol. 8   page: 326   2019.8

     More details

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

    DOI: 10.3390/antiox8090326

  10. Structural and functional insights into S-thiolation of human serum albumins Reviewed International coauthorship

    Nakashima F, Shibata T, Kamiya K, Yoshitake J, Kikuchi R, Matsushita T, Ishii I, Giménez-Bastida JA, Schneider C, Uchida K

      Vol. 8   page: 932   2018.1

     More details

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

    DOI: 10.1038/s41598-018-19610-9

  11. Adductome-based identification of biomarkers for lipid peroxidation Reviewed

    Shibata T, Shimizu K, Hirano K, Nakashima F, Kikuchi R, Matsushita T, Uchida K

    Journal of Biological Chemistry   Vol. 292 ( 2 ) page: 8223 - 8235   2017.3

     More details

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

    DOI: 10.1074/jbc.M116.762609

  12. Oxidative metabolism of curcumin-glucuronide by peroxidases and isolated human leukocytes Reviewed International coauthorship

    Luis PB, Gordon ON, Nakashima F, Joseph AI, Shibata T, Uchida K, Schneider C

    Biochemical Pharmacology   Vol. 132   page: 143 - 149   2017.3

     More details

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

    DOI: doi.org/10.1016/j.bcp.2017.03.002

  13. Oxidative deamination of serum albumins by (-)-epigallocatechin-3-O-gallate: A potential mechanism for the formation of innate antigens by antioxidants Reviewed

    Hatasa Y, Chikazawa M, Furuhashi M, Nakashima F, Shibata T, Kondo T, Akagawa M, Hamagami H, Tanaka H, Tachibana H, Uchida K

    PLoS One   Vol. 11 ( 4 ) page: e0153002   2016.4

     More details

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

    DOI: 10.1371/journal.pone.0153002

  14. Identification of a prostaglandin D2 metabolite as a neuritogenesis enhancer targeting the TRPV1 ion channel Reviewed

    Shibata T, Takahashi K, Matsubara Y, Inuzuka E, Nakashima F, Takahashi N, Kozai D, Mori Y, Uchida K

    Scientific Reports   Vol. 6   page: 21261   2016.2

     More details

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

    DOI: 10.1038/srep21261

  15. Identification of C1q as a binding protein for advanced glycation end products Reviewed

    Chikazawa M, Shibata T, Hatasa Y, Hirose S, Otaki N, Nakashima F, Ito M, Machida S, Maruyama S, Uchida K

    Bochemistry   Vol. 55   page: 435 - 446   2016.1

     More details

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

    DOI: 10.1021/acs.biochem.5b00777

  16. Functional interaction between cyclooxygenase-2 and p53 in response to an endogenous electrophile Reviewed

    Kumagai T, Usami H, Matsukawa N, Nakashima F, Chikazawa M, Shibata T, Noguchi N, Uchida K

    Redox Biology   Vol. 4   page: 74 - 86   2014.12

     More details

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

    DOI: doi.org/10.1016/j.redox.2014.11.011

  17. Toll-like receptors as a target of food-derived anti-inflammatory compounds Reviewed

    Shibata T, Nakashima F, Honda K, Lu YJ, Kondo T, Ushida Y, Aizawa K, Suganuma H, Oe S, Tanaka H, Takahashi T, Uchida K

    Journal of Biological Chemistry   Vol. 289 ( 47 ) page: 32757 - 32772   2014.11

     More details

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

    DOI: 10.1074/jbc.M114.585901

  18. Lysine pyrrolation is a naturally-occurring covalent modification involved in the production of DNA mimic proteins Reviewed

    Miyashita H, Chikazawa M, Otaki N, Hioki Y, Shimozu Y, Nakashima F, Shibata T, Hagihara Y, Maruyama S, Matsumi N, Uchida K

      Vol. 4   page: 5343   2014.6

     More details

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

    DOI: 10.1038/srep05343

▼display all

Books 3

  1. 実験医学増刊「食と健康を結ぶメディカルサイエンス 生体防御系を亢進し、健康の維持に働く分子機構」

    中島史恵、柴田貴広、内田浩二( Role: Joint author ,  システイン残基のユニークな自然修飾)

    羊土社  2020  ( ISBN:978-4-7581-0387-9

     More details

    Responsible for pages:52-58   Language:Japanese Book type:Scholarly book

  2. 実験医学「レドックス疾患学」

    中島史恵、柴田貴広、内田浩二( Role: Joint author ,  脂質異常症に関連したタンパク質のS-チオール化)

    羊土社  2018  ( ISBN:978-4-7581-0369-5

     More details

    Responsible for pages:264-270   Language:Japanese Book type:Scholarly book

  3. ケルセチン及びケルセチン配糖体によるToll様受容体シグナリング抑制 Reviewed

    中島史恵、柴田貴広、内田浩二( Role: Joint author)

    日本ポリフェノール学会雑誌  2016 

     More details

    Responsible for pages:38-42   Language:Japanese

KAKENHI (Grants-in-Aid for Scientific Research) 3

  1. 疾患状態を反映する代謝物アダクトームの解明

    Grant number:23K17449  2023.6 - 2027.3

    日本学術振興会  科学研究費助成事業  挑戦的研究(開拓)

    柴田 貴広, 中島 史恵, 三城 恵美, 服部 浩之, 中島 史恵, 佐藤恵美, 服部 浩之

      More details

    Authorship:Coinvestigator(s) 

    疾患状態に起因する内因性代謝物や食品由来成分の代謝物の一部が、生体内のタンパク質に様々な付加体(アダクト)を形成していることが知られている。生体内タンパク質における代謝物アダクトの総体「代謝物アダクトーム」を明らかにすることができれば、ヒトの生体内環境や疾患状態を理解・評価できると考えられる。本研究では、代謝物アダクトーム解析法を確立し、生体内の状態や疾患状態を反映する代謝物アダクトの同定に挑戦する。

    researchmap

  2. 新規エイコサノイドhemiketal E2によるタンパク質修飾を介した血管新生機構の解明

    Grant number:23K13881  2023.4 - 2025.3

    日本学術振興会  科学研究費助成事業  若手研究

    中島 史恵

      More details

    Authorship:Principal investigator 

    Grant amount:\4680000 ( Direct Cost: \3600000 、 Indirect Cost:\1080000 )

    Hemiketal E2は機能未知のアラキドン酸由来生理活性脂質であり、研究代表者は、HKE2が血管内皮細胞においてvascular endothelial growth factor receptor 2のリン酸化を介して血管新生を誘導することを明らかにしてきた。しかし、その詳細なメカニズムは不明である。本研究では、HKE2の化学的特性から「Cys残基がHKE2によって修飾された特定のタンパク質が血管新生に関与する」という仮説を立て、これを検証する。

    researchmap

  3. 脂質酸化酵素のクロストークにより産生される新規生理活性脂質の探索

    Grant number:22K20570  2022.8 - 2024.3

    日本学術振興会  科学研究費助成事業 研究活動スタート支援  研究活動スタート支援

    中島 史恵

      More details

    Authorship:Principal investigator 

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

    アラキドン酸は、リポキシゲナーゼ (LOX) 経路もしくはシクロオキシゲナーゼ (COX) 経路の2つの古典的経路によりエイコサノイドへと代謝され、炎症や組織の恒常性維持において中心的役割を果たす。しかし、慢性炎症性疾患の発症を既知のエイコサノイドの生合成阻害では完全に抑制できないことから、古典的経路で生合成されるエイコサノイドだけでは全ての生体応答を説明することができず、アラキドン酸代謝経路の全容解明が求められている。そこで本研究では、”5-LOX/COX-2クロストーク”により生成される新規エイコサノイドの探索と、その生理活性の解明を目指す。
    標品5-OH-thromboxane B2の作製を行った。作製には一重項酸素付加反応を用い、thromboxane B2と光増感剤であるメチレンブルーを4℃にて一晩反応させた。サンプルをHPLCにより分析・精製した後、質量分析装置による解析を行った結果、 thromboxane B2の5位の炭素にOH基を有する5-OH-thromboxane B2の生成が確認された。さらに、精製した標品5-OH-thromboxane B2を用いて、質量分析装置による検出の最適化を行い、5-OH-thromboxane B2の定量方法を確立した。
    5-OH-thromboxane B2を検出するin vitroの系の確立を行った。5-OH-thromboxane B2の産生に必要な酵素である5-リポキシゲナーゼ、シクロオキシゲナーゼ-2、トロンボキサン合成酵素の3つの酵素の発現が期待されるヒト血液由来細胞であるHL-60を用いて検討を行った。DMSOを4日間処理し、成熟顆粒球へと分化させたのち、LPS刺激によりシクロオキシゲナーゼ-2の発現を誘導した結果、シクロオキシゲナーゼ-2により産生されるprostaglandin E2/D2、トロンボキサン合成酵素によって産生されるthromboxane B2の生成が確認された。また、カルシウムイオノフォア刺激により、5-リポキシゲナーゼにより産生されるleukotriene B4の生成が確認された。これらのことから、成熟顆粒球へと分化させたHL-60に適切な刺激を行うことで、5-OH-thromboxane B2の産生に必要な酵素である5-リポキシゲナーゼ、シクロオキシゲナーゼ-2、トロンボキサン合成酵素の三つの酵素を発現することが明らかとなり、成熟顆粒球へと分化させたHL-60がin vitroモデルとして使用可能であることを確認した。
    当初の計画通り、一重項酸素付加反応を用いて標品5-OH-thromboxane B2を作製することができた。またin vitro のモデルとして使用するヒト血液由来培養細胞の選定ができた。
    刺激した分化ヒト血液由来培養細胞から5-OH-thromboxane B2の検出・定量を行う。合わせて5-OH-thromboxane B2の生理活性の評価を進めていく予定である。

    researchmap

 

Teaching Experience (On-campus) 4

  1. Chemical Biology

    2023

  2. 応用生命科学科実験実習

    2023

  3. Chemical Biology

    2022

  4. 応用生命科学科実験実習

    2022