Updated on 2026/06/16

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 Interests 3

  1. Inflammation

  2. Bioactive Lipid

  3. 食品機能化学

Research Areas 3

  1. Life Science / Food sciences

  2. Life Science / Pharmacology  / bioactive lipids

  3. Life Science / Food sciences

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

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    Country:Japan

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  2. Vanderbilt University Medical School   Researcher

    2018.11 - 2022.1

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    Country:United States

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  3. Nagoya University   Graduat   Researcher

    2018.3 - 2018.11

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    Country:Japan

  4. Japan Society for Promotion of Science   Researcher

    2016.4 - 2018.3

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    Country:Japan

Education 3

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

    2015.4 - 2018.3

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    Country: Japan

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

    2013.4 - 2015.3

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    Country: Japan

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

    2009.4 - 2013.3

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    Country: Japan

Professional Memberships 2

  1. 日本生化学会

    2014.9

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  2. 日本農芸化学会

    2013.3

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Committee Memberships 2

  1. 日本生化学会中部支部   第3グループ幹事  

    2024.9 - 2026.8   

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    Committee type:Academic society

  2. 日本農芸化学会中部支部   会計幹事  

    2024.4 - 2026.3   

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    Committee type:Academic society

Awards 4

  1. 農芸化学若手女性研究者賞

    2026.3   日本農芸化学会   食品由来成分の抗炎症機能に関する分子基盤の解析

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

  2. ONO Pharmaceutical Travel Awards for Japanese Young Investigator

    2019.10   ONO PHARMACEUTICAL CO., LTD.  

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    Award type:Award from international society, conference, symposium, etc.  Country:United States

  3. Cayman Chemical Company Research Travel Award

    2019.10  

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    Award type:Award from international society, conference, symposium, etc.  Country:United States

  4. 名古屋大学学術奨励賞受賞

    2017.6   名古屋大学  

 

Papers 29

  1. A missense mutation in acyl-CoA synthetase ACSL4 reveals essential residues for catalytic activity in ferroptosis Reviewed Open Access

    Haruka Sei, Harumi Ando, Fumie Nakashima, Terunao Takahara, Masaki Kita, Ken-ichi Yamada, Koji Uchida, Takahiro Shibata

    Journal of Biological Chemistry   Vol. 302 ( 3 ) page: 111232   2026.3

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    DOI: 10.1016/j.jbc.2026.111232

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  2. Dietary anthocyanidin pelargonidin activates G protein-coupled receptor 35. Reviewed International journal Open Access

    Fumie Nakashima, Sayako Shimomura, Mayuka Wakabayashi, Wei Qi Loh, Harumi Ando, Haruka Sei, Hiroyuki Hattori, Didik Huswo Utomo, Masaki Kita, Asuka Inoue, Koji Uchida, Takahiro Shibata

    The FEBS journal   Vol. 293 ( 5 ) page: 1386 - 1399   2026.3

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    G protein-coupled receptors (GPCRs) are the largest superfamily of cell surface receptors. They regulate critical physiological events and serve as potential therapeutic targets. G protein-coupled receptor 35 (GPR35), a class A rhodopsin-like GPCR expressed in various tissues, including adipose tissue and the gastrointestinal tract, has roles in diverse functions, including antioxidant, anticarcinogenic, and anti-inflammatory effects. Although many endogenous and synthetic GPR35 agonists have been identified, the understanding of food-derived agonists is limited. In this study, we discovered pelargonidin as a newly identified food-derived GPR35 agonist through a systematic screening approach. We evaluated 28 dietary phytochemicals using a transforming growth factor α (TGFα) shedding assay to evaluate GPR35 activation, and found that cyanidin, a common 3-hydroxyanthocyanidin present in various red fruits and vegetables, induced GPR35 activation. Among a series of 3-hydroxyanthocyanidins tested, pelargonidin, characterized by its monohydroxylated B-ring, exhibited the most potent agonistic activity. Mutational studies demonstrated that the hydrogen bond between the 3-hydroxy group in the C-ring of pelargonidin and Asn169, as well as the hydrophobic interaction between the A-ring of pelargonidin and Phe163, is crucial for GPR35 activation. Furthermore, pelargonidin inhibited the production of interleukin-8, a pro-inflammatory cytokine, by activating endogenous GPR35 in Caco-2 cells. These findings suggest that GPR35 may serve as a potential receptor for dietary anthocyanidins, such as pelargonidin, and provide new insights into the molecular mechanisms underlying the potential chemopreventive effects of anthocyanidins.

    DOI: 10.1111/febs.70311

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  3. Oral administration of pomegranate juice enhances antioxidant defense and reduces tyrosinase activity in mouse skin Open Access

    Washiya Yuki, Sei Haruka, Nakashima Fumie, Shibata Takahiro, Fujino Tsuchiyoshi

    Food Science and Technology Research   Vol. advpub ( 0 )   2026

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:Japanese Society for Food Science and Technology  

    <p>Pomegranate juice, which is rich in polyphenols and ellagitannins, has antioxidant and anti-inflammatory properties. The potential skin-protective effects of these polyphenols have garnered increasing attention in dermatological research. Therefore, we investigated the effects of its oral intake on skin health in mice. Mice were orally administered pomegranate juice for 14 days, and skin biochemical parameters were subsequently analyzed. Pomegranate juice intake significantly reduced skin tyrosinase activity and pro-inflammatory cytokine levels. In addition, the activities of antioxidant enzymes, including catalase and glutathione peroxidase, significantly increased in the skin. Total phenolic content in the skin was significantly elevated. Targeted mass spectrometric analysis revealed significant increases in ellagic acid and gallic acid in the skin. Overall, these findings suggest that oral pomegranate juice intake supports the maintenance of skin homeostasis by modulating melanogenic, inflammatory, and oxidative pathways. This study could facilitate the use of pomegranate-derived compounds in functional foods aimed at promoting skin health.</p>

    DOI: 10.3136/fstr.fstr-d-26-00010

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  4. Structural and Functional Basis of G Protein-Coupled Receptor 35 Activation by Pyrroloquinoline Quinone. Reviewed International journal

    Harumi Ando, Akari Kanamori, Mayuka Wakabayashi, Fumie Nakashima, Haruka Sei, Hiroyuki Hattori, Masaki Kita, Asuka Inoue, Ayana Murakami, Mitsugu Akagawa, Koji Uchida, Takahiro Shibata

    Biochemistry   Vol. 64 ( 24 ) page: 4758 - 4767   2025.12

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    Pyrroloquinoline quinone (PQQ), an o-quinone-type nutrient, has been shown to exert diverse beneficial effects on the biochemical and physiological processes of mammals. However, the molecular mechanisms underlying these effects remain incompletely understood. Here, through screening of metabolite-sensing G protein-coupled receptors (GPCRs)─which respond to metabolites produced by gut microbiota or derived from nutrients─we found that PQQ selectively activates G-protein-coupled receptor 35 (GPR35) and characterized the molecular basis of its ligand recognition. Using a transforming growth factor α shedding assay, we demonstrated that PQQ selectively activated GPR35, a class A rhodopsin-like GPCR expressed in various tissues, including adipose tissue and the gastrointestinal tract. PQQ also promoted β-arrestin 1 recruitment to the plasma membrane, further supporting its role as a GPR35 agonist. Direct binding of PQQ to GPR35 was demonstrated using a clickable photoaffinity probe derived from PQQ. Molecular docking simulation and site-directed mutagenesis revealed that the 2-carboxylic acid moiety of PQQ forms critical hydrogen bonds with Arg100, Tyr101, and Arg151 of GPR35. Additionally, Phe163 appears to contribute to π-H interaction with PQQ. These findings indicate that PQQ functions as a food-derived agonist of GPR35 and provide new insights into the molecular mechanisms underlying the potential beneficial effects of PQQ.

    DOI: 10.1021/acs.biochem.5c00566

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  5. Adductome-based identification of lysine monomethylation as a key post-translational protein modification in autoimmune diseases. Reviewed International journal Open Access

    Kosuke Yamaguchi, You-Yun Hu, Kaito Kawajiri, Masanori Itakura, Fumie Nakashima, Takahiro Shibata, Koji Uchida

    The Journal of biological chemistry   Vol. 301 ( 10 ) page: 110684 - 110684   2025.10

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    Post-translational modifications (PTMs) of proteins are efficient biological mechanisms for expanding the genetic code and for regulating cellular physiology. However, there have been no systematic approaches to profile all the PTMs critical for autoreactive neoantigen production or the etiology and pathology of autoimmune diseases. In the present study, to gain insight into protein PTMs associated with systemic lupus erythematosus (SLE), we applied a mass spectrometry-based method for the comprehensive analysis of modified amino acids ("adductome"). By comprehensively measuring modified lysines and histidines in mouse tissue homogenates from the control and SLE-prone MRL-lpr mice, we observed a significant decrease in lysine monomethylation as a unique alteration in the PTMs of SLE mice splenocytes. One of the targets for the downregulation of lysine monomethylation was identified as histone H3. Downregulation of histone H3 lysine 4 monomethylation (H3K4me1) was also observed in the B cells from SLE mice. Inhibition of the H3K4me1 demethylase LSD1 suppressed the differentiation of naive B cells into antibody-secreting cells. In addition, the reduction of H3K4me1 in SLE mice resulted in the downregulation of PAX5, a transcription factor indispensable for the maturation of B cells, leading to the activation of antibody-secreting cells. The results of this study suggest that dysregulation of histone lysine monomethylation may play a significant role in the pathophysiology of SLE and therefore may be a target for epigenetic-based lupus treatment.

    DOI: 10.1016/j.jbc.2025.110684

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  6. The origin of hydroxy-cyclohexenone fatty acids from skin barrier protein and relevance to covalent binding of ceramides Reviewed International coauthorship International journal Open Access

    Saori Noguchi, William E. Boeglin, Fumie Nakashima, Donald F. Stec, M. Wade Calcutt, Takuya Takeichi, Masashi Akiyama, Alan R. Brash

    Journal of Lipid Research   Vol. 66 ( 7 ) page: 100843 - 100843   2025.7

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    Lipid constituents of the skin permeability barrier include a portion of ceramides and fatty acids covalently bound to the barrier protein. The covalent binding requires enzymatic oxidation of linoleate (C18:2) esterified to skin-specific acylceramides, forming a reactive 9,10-epoxy-11E-13-keto derivative. Barrier proteins treated with alkali release the bound lipids and as described recently, including two prominent cyclic linoleate derivatives, C18 hydroxy-cyclohexenone fatty acids. Herein we addressed the origin of these cyclic products by alkali treatment of potential precursors. A UV-based assay indicated the rates of Michael adduction of 9,10-epoxy-11E-13-keto to cysteine are two orders of magnitude faster than for a typical unsaturated keto fatty acid, and 10-fold faster for the dihydroxy analogue, rationalizing their biosynthesis for protein adduction. Alkali treatment degraded the epoxy-ketone and its cysteinyl (glutathione) adduct to multiple UV-absorbing products, although not including the hydroxy-cyclohexenones. By contrast, these derivatives were prominently produced from KOH treatment of the 9,10-dihydroxy-13-ketone or its glutathione adduct. As further evidence of the origin of the hydroxy-cyclohexenones, LC-MS quantitation showed a 90% reduction following KOH treatment of epidermis from mice deficient in Srd9c7, the dehydrogenase in the linoleate oxidation pathway. Taken together, the results confirm the hydroxy-cyclohexenones as derivatives of the linoleate oxidations in the skin barrier pathway and identify the dihydroxy-ketone as a component of the covalently-bonded lipids, and critical to integrity of the epidermal barrier.

    DOI: 10.1016/j.jlr.2025.100843

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  7. 酸化により発揮されるクルクミンの機能性(若手特別講演) Open Access

    中島 史恵

    ビタミン   Vol. 99 ( 3 ) page: 220 - 221   2025

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    Language:Japanese   Publisher:公益社団法人 日本ビタミン学会  

    DOI: 10.20632/vso.99.3_220

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  8. Dry Heating of Curcumin in the Presence of Basic Salts Yields Anti-inflammatory Dimerization Products Reviewed International coauthorship Open Access

    Paula B. Luis, Fumie Nakashima, Sai Han Presley, Gary A. Sulikowski, Claus Schneider

    ACS Omega   Vol. 9 ( 35 ) page: 37025 - 37034   2024.8

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    DOI: 10.1021/acsomega.4c03257

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  9. Seabuckthorn (<i>Hippophae rhamnoides</i>, L.) pulp oil prevents ultraviolet-induced damage in human fibroblasts Reviewed Open Access

    Takuya Okamoto, Fumie Nakashima, Takahiro Shibata, Daisuke Mori

    Bioscience, Biotechnology, and Biochemistry   Vol. 88 ( 8 ) page: 948 - 955   2024.6

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:Oxford University Press (OUP)  

    ABSTRACT

    Seabuckthorn pulp oil (SBO) is used in beauty products because of its rich lipophilic substances with high nutraceutical and cosmeceutical potential. However, the mechanism through which SBO enhances skin elasticity remains unclear. Therefore, in this study, we examined the anti-photoaging activity of SBO in normal human dermal fibroblasts (NHDF) under ultraviolet (UV) irradiation. Pretreatment with SBO significantly suppressed UV-B-induced cell toxicity and collagen degradation, suggesting that SBO contains anti-photoaging substances. Further, palmitoleic acid, the main component of SBO, maintained cell viability and collagen levels in UV-B-irradiated NHDF by suppressing the expression of matrix metalloproteinase 1 and acted on the inhibition of p38 and JNK phosphorylation and nuclear translocation of nuclear factor-kappa B. These findings suggest the utility of SBO as an anti-photoaging agent.

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    Other Link: https://academic.oup.com/bbb/article-pdf/88/8/948/58607660/zbae071.pdf

  10. Isocitrate dehydrogenase 1 upregulation in urinary extracellular vesicles from proximal tubules of type 2 diabetic rats Reviewed International journal Open Access

    Haruka Sei, Naoya Hirade, Kohei Kamiya, Fumie Nakashima, Jun Yoshitake, Keiko Kano, Emi Mishiro‐Sato, Ryosuke Kikuchi, Koji Uchida, Takahiro Shibata

    The FASEB Journal   Vol. 38 ( 10 ) page: e23688   2024.5

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    Diabetic nephropathy (DN) is a major cause of chronic kidney disease. Microalbuminuria is currently the most common non‐invasive biomarker for the early diagnosis of DN. However, renal structural damage may have advanced when albuminuria is detected. In this study, we sought biomarkers for early DN diagnosis through proteomic analysis of urinary extracellular vesicles (uEVs) from type 2 diabetic model rats and normal controls. Isocitrate dehydrogenase 1 (IDH1) was significantly increased in uEVs from diabetic model rats at the early stage despite minimal differences in albuminuria between the groups. Calorie restriction significantly suppressed the increase in IDH1 in uEVs and 24‐hour urinary albumin excretion, suggesting that the increase in IDH1 in uEVs was associated with the progression of DN. Additionally, we investigated the origin of IDH1‐containing uEVs based on their surface sugar chains. Lectin affinity enrichment and immunohistochemical staining showed that IDH1‐containing uEVs were derived from proximal tubules. These findings suggest that the increase in IDH1 in uEVs reflects pathophysiological alterations in the proximal tubules and that IDH1 in uEVs may serve as a potential biomarker of DN in the proximal tubules.

    DOI: 10.1096/fj.202400371R

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  11. Contribution of Covalent Modification of Food-derived Compounds to Anti-inflammatory Activities

    Nakashima Fumie, Shibata Takahiro, Uchida Koji

    Nippon Eiyo Shokuryo Gakkaishi   Vol. 77 ( 2 ) page: 125 - 130   2024

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    <p>As chronic inflammation is known to lead to serious diseases such as cancer and diabetes, proper control of inflammatory responses is essential for maintenance of health. A wide variety of food-derived low-molecular-weight compounds is known to possess bioactivities such as anti-inflammatory, antioxidant, and anti-tumor activity. Long experience has shown that certain foods have health benefits, but the molecular mechanisms by which food-derived low-molecular-weight compounds exert their bioactivity have remained unclear. By focusing on the electrophilic activity of food-derived compounds, we have identified several proteins as target molecules for the anti-inflammatory activity of food-derived low-molecular-weight compounds. Here we review the anti-inflammatory activity of iberin from cabbage and curcumin from turmeric.</p>

    DOI: 10.4327/jsnfs.77.125

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  12. 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

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    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 of 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 2 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

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

    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

    Journal of Biological Chemistry   Vol. 299 ( 4 ) page: 103050 - 103050   2023.4

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    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

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  14. Biosynthetic Crossover of 5-Lipoxygenase and Cyclooxygenase-2 Yields 5-Hydroxy-PGE<sub>2</sub> and 5-Hydroxy-PGD<sub>2</sub> Reviewed International coauthorship Open Access

    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

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    DOI: 10.1021/jacsau.1c00177

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

    Moeri Oshimo, Fumie Nakashima, Kenji Kai, Hirofumi Matsui, Takahiro Shibata, Mitsugu Akagawa

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

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    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.

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

    Rebecca L. Edwards, Paula B. Luis, Fumie Nakashima, Andrew G. Kunihiro, Sai-Han Presley, Janet L. Funk, Claus Schneider

    Journal of Agricultural and Food Chemistry   Vol. 68 ( 22 ) page: 6154 - 6160   2020.5

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    DOI: 10.1021/acs.jafc.0c02607

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

    Fumie Nakashima, Claus Schneider

    Lipids   Vol. 55 ( 1 ) page: 73 - 78   2019.12

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    DOI: 10.1002/lipd.12206

  18. A unique mechanism for thiolation of serum albumins by disulphide molecules Invited Reviewed Open Access

    Fumie Nakashima, Takahiro Shibata, Koji Uchida

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

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    DOI: 10.1093/jb/mvz084

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

    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

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

  20. 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 Open Access

    Ana Martin-Rubio, Patricia Sopelana, Fumie Nakashima, Takahiro Shibata, Koji Uchida, María Guillén

    Antioxidants   Vol. 8 ( 9 ) page: 326 - 326   2019.8

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    DOI: 10.3390/antiox8090326

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

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

    Scientific Reports   Vol. 8 ( 1 )   2018.1

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    DOI: 10.1038/s41598-018-19610-9

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  22. Adductome-based identification of biomarkers for lipid peroxidation Reviewed Open Access

    Takahiro Shibata, Kazuma Shimizu, Keita Hirano, Fumie Nakashima, Ryosuke Kikuchi, Tadashi Matsushita, Koji Uchida

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

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    DOI: 10.1074/jbc.M116.762609

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

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

    Biochemical Pharmacology   Vol. 132   page: 143 - 149   2017.3

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

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

    Yukinori Hatasa Miho Chikazawa Mai Furuhashi Fumie Nakashima Takahiro Shibata Tatsuhiko Kondo Mitsugu Akagawa Hiroki Hamagami Hiroshi Tanaka Hirofumi Tachibana Koji Uchida

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

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    DOI: 10.1371/journal.pone.0153002

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

    Takahiro Shibata, Katsuhiro Takahashi, Yui Matsubara, Emi Inuzuka, Fumie Nakashima, Nobuaki Takahashi, Daisuke Kozai, Yasuo Mori, Koji Uchida

    Scientific Reports   Vol. 6   page: 21261   2016.2

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    DOI: 10.1038/srep21261

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

    Miho Chikazawa, Takahiro Shibata, Yukinori Hatasa, Sayumi Hirose, Natsuki Otaki, Fumie Nakashima, Mika Ito, Sachiko Machida, Shoichi Maruyama, Koji Uchida

    Bochemistry   Vol. 55   page: 435 - 446   2016.1

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    DOI: 10.1021/acs.biochem.5b00777

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

    Takeshi Kumagai, Hiroko Usami, Nao Matsukawa, Fumie Nakashima, Miho Chikazawa, Takahiro Shibata, Noriko Noguchi, Koji Uchida

    Redox Biology   Vol. 4   page: 74 - 86   2014.12

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

    Open Access

  28. Toll-like receptors as a target of food-derived anti-inflammatory compounds Reviewed Open Access

    Takahiro Shibata Fumie Nakashima Kazuya Honda Yu-Jhang Lu Tatsuhiko Kondo Yusuke Ushida Koichi Aizawa Hiroyuki Suganuma Sho Oe Hiroshi Tanaka Takashi Takahashi Koji Uchida

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

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

    DOI: 10.1074/jbc.M114.585901

    Open Access

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

    Hiroaki Miyashita Miho Chikazawa Natsuki Otaki Yusuke Hioki Yuki Shimozu Fumie Nakashima Takahiro Shibata Yoshihisa Hagihara Shoichi Maruyama Noriyoshi Matsumi Koji Uchida

      Vol. 4 ( 1 )   2014.6

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

    DOI: 10.1038/srep05343

    Open Access

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Books 2

  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」

    内田浩二( Role: Contributor ,  システイン残基のユニークなS-チオール化)

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

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

  2. レドックス疾患学 : 酸素・窒素・硫黄活性種はどう作用するのか、どこまで健康・疾患と関わるのか?

    赤池, 孝章 , 本橋, ほづみ , 内田, 浩二 , 末松, 誠( Role: Contributor ,  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

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

MISC 3

  1. Contribution of Covalent Modification of Food-derived Compounds to Anti-inflammatory Activities Invited Reviewed

    Fumie Nakashima , Takahiro Shibata , Koji Uchida

    Nippon Eiyo Shokuryo Gakkaishi   Vol. 77 ( 2 ) page: 125 - 130   2024

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    Authorship:Lead author   Language:English   Publishing type:Article, review, commentary, editorial, etc. (scientific journal)  

    DOI: 10.4327/jsnfs.77.125

  2. Novel eicosanoids from the COX-2 reaction: 5-hydroxy-prostaglandins Invited International coauthorship

    Fumie Nakashima, Claus Schneider

    ASBMB Today     page: 20 - 21   2022.6

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    Language:English   Publishing type:Article, review, commentary, editorial, etc. (trade magazine, newspaper, online media)  

  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 Invited Reviewed

    中島史恵 , 柴田貴広 , 内田浩二

    日本ポリフェノール学会雑誌   Vol. 5 ( 1 ) page: 38 - 42   2016.7

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

Presentations 27

  1. 酸化型クルクミンによるタンパク質修飾と炎症応答制御機構の解明

    山岡 美晶、發知 繭、柴田 貴広、中島 史恵

    日本農芸化学会2026年度大会  2026.3.11  日本農芸化学会

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    Event date: 2026.3

    Language:Japanese  

    Venue:京都   Country:Japan  

  2. Oxidative transformation induces a gain of function in curcumin Invited

    Fumie Nakashima, Takahiro Shibata

    JSBBA Annual Meeting 2026  2026.3.11  JSBBA

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    Event date: 2026.3

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

    Venue:Kyoto   Country:Japan  

  3. 酵素の協調的作用により生成される生理活性脂質に関する研究

    行川朋花, 柴田貴広, 中島史恵

    第98回日本生化学会大会  2025.11 

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    Event date: 2025.11

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  4. アレルギー応答時に産生されるヘミケタール類に関する研究

    中島史恵, 日向宏成, 安藤凛香, 柴田貴広

    第98回日本生化学会大会  2025.11 

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    Event date: 2025.11

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  5. 酸化により発揮されるクルクミンの機能性 Invited

    中島史恵

    日本ビタミン学会第77回大会  2025.6.28 

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    Event date: 2025.6

    Presentation type:Symposium, workshop panel (public)  

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  6. 酸化によって発揮される食品成分の機能性 Invited

    中島史恵

    2025プラズマの日(プラズマサミット in 岐阜)  2025.6.20 

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    Event date: 2025.6

    Presentation type:Symposium, workshop panel (nominated)  

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  7. 脂質酸化酵素の協調的作用により生成される新奇生理活性脂質 Invited

    中島史恵

    レドックスR&D戦略委員会 第5回春のシンポジウム  2025.3.15 

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    Event date: 2025.3

    Presentation type:Symposium, workshop panel (nominated)  

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  8. アレルギー応答時に産生される新奇脂質メディエーターに関する研究

    中島 史恵, 日向 宏成, 柴田 貴広

    日本農芸化学会2025年度大会  2025.3.7 

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    Event date: 2025.3

    Presentation type:Poster presentation  

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  9. フラボノイドによるGPR35の活性化

    中島史恵, 下村沙也子, 安藤春美, 井上飛鳥, 内田浩二, 柴田貴広

    第97回日本生化学会大会  2024.11.6 

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    Event date: 2024.11

    Presentation type:Oral presentation (general)  

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  10. 肥満細胞におけるCOX-2と5-LOXの協調的作用の解析

    日向宏成, 中島史恵, 内田浩二, 柴田貴広

    第97回日本生化学会大会  2024.11.8 

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    Event date: 2024.11

    Presentation type:Poster presentation  

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  11. 細胞外小胞に含まれるエイコサノイドの解析

    浅井莉子, 中島史恵, 柴田貴広

    第97回日本生化学会大会  2024.11.8 

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    Event date: 2024.11

    Presentation type:Poster presentation  

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  12. クルクミン酸化的変換産物の標的タンパク質の探索

    發知繭, 中島史恵, 柴田貴広

    日本農芸化学会 中部支部第199回例会  2024.9.28 

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    Event date: 2024.9

    Presentation type:Poster presentation  

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  13. 酵素の協調的作用により生成される生理活性脂質に関する研究

    行川朋花, 中島史恵, 柴田貴広

    日本農芸化学会 中部支部第199回例会  2024.9.28 

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    Event date: 2024.9

    Presentation type:Poster presentation  

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  14. Oxidative transformation gives function to food-derived low-molecular compounds Invited

    Fumie Nakashima

    jsot2024  2024.7.5 

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    Event date: 2024.7

    Language:English  

    Venue:福岡   Country:Japan  

  15. 細胞外小胞に含まれるエイコサノイドの解析

    浅井莉子, 中島史恵, 柴田貴広

    第88回 日本生化学会 中部支部例会・シンポジウム  2024.5.25 

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    Event date: 2024.5

    Presentation type:Poster presentation  

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  16. アラキドン酸由来生理活性脂質HKE2の血管新生活性 International coauthorship

    中島史恵, Luis Paula, Presley SaiHan, 柴田貴広, Pozzi Ambra, Schneider Claus

    第96回日本生化学会大会  2023.10.31 

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    Event date: 2023.10 - 2023.11

    Language:Japanese   Presentation type:Poster presentation  

  17. クルクミンによる抗炎症メカニズムの解明:活性本体としてのクルクミン酸化物の同定

    發知繭, 中島史恵, 柴田貴広, 柴田貴広, 柴田貴広

    日本農芸化学会 中部・関西支部合同大会  2023.9.30 

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    Event date: 2023.9 - 2023.10

    Presentation type:Oral presentation (general)  

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  18. 腸管上皮細胞におけるクルクミンの炎症抑制メカニズムの解明

    中島史恵, 生駒鋼樹, Luis Paula, 服部浩之, Schneider Claus, 内田浩二

    日本農芸化学会2023年度大会  2023.3.15 

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    Event date: 2023.3

    Language:Japanese   Presentation type:Oral presentation (general)  

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  19. Cyclooxygenase-2および5-Lipoxygenaseのクロストークにより産生される新規プロスタグランジンの同定 International coauthorship

    第95回日本生化学会大会  2022.11.10  日本生化学会

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    Event date: 2022.11

    Language:Japanese   Presentation type:Oral presentation (general)  

    Venue:名古屋   Country:Japan  

  20. The 5-LOX/COX-2 cross-over eicosanoid, HKE2, is a novel regulator of endothelial cell angiogenesis International coauthorship International conference

    Fumie Nakashima, Juan A. Giménez-Bastida, Sai H. Presley, Ambra Pozzi, Claus Schneider

    The 18th International Winter Eicosanoid Conference  2020.9  Eicosanoid Research Association, Inc.

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    Event date: 2020

    Language:English   Presentation type:Oral presentation (general)  

    Venue:Baltimore   Country:United States  

  21. The 5-LOX/COX-2 cross-over eicosanoid, HKE2, is a novel regulator of endothelial cell angiogenesis International coauthorship International conference

    Fumie Nakashima, Juan A. Giménez-Bastida, Sai H. Presley, Ambra Pozzi, Claus Schneider

    16th International Conference on Bioactive Lipids in Cancer, Inflammation, and Related Diseases  2019.10  Eicosanoid Research Foundation

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    Event date: 2019

    Language:English   Presentation type:Poster presentation  

    Venue:St. Petersburg, Florida   Country:United States  

  22. Identification of an endogenous COX-2 inducer in human serum International conference

    Fumie Nakashima, Takahiro Shibata, Koji Uchida

    The 16th International Winter Eicosanoid Conference  2016.2  Eicosanoid Research Association, Inc.

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    Event date: 2016

    Language:English   Presentation type:Poster presentation  

    Venue:Baltimore   Country:United States  

  23. Biosynthetic crossover of 5-lipoxygenase and cyclooxygenase-2 yields novel eicosanoids

    Fumie Nakashima

    NRCT-JSPS Bilateral Joint Research Meeting  2026.3.20 

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  24. Oxidative transformation induces a gain of function in curcumin Invited

    Fumie Nakashima, Takahiro Shibata

    Japan-Taiwan International Joint Symposium on Food Science, JSBBA Annual Meeting 2026  2026.3.11 

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  25. アレルギー応答時に生成される新奇脂質メディエーターの解析

    安藤凜香, 中島史恵, 柴田貴広

    日本農芸化学会中部支部第202回例会  2025.9.20 

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  26. クルクミンはIKKβへの修飾を介して炎症を抑制する

    發知繭, 柴田貴広, 中島史恵

    日本農芸化学会中部支部第202回例会  2025.9.20 

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  27. 酸化型クルクミンによるタンパク質修飾と炎症応答制御機構の解明

    山岡 美晶, 發知 繭, 柴田 貴広, 中島 史恵

    日本農芸化学会2026年度京都大会  2026.3.11 

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Research Project for Joint Research, Competitive Funding, etc. 2

  1. ターメリックの主要成分クルクミンのもつ未知機能の解明

    2025.4 - 2026.3

    公益財団法人ロッテ財団 奨励研究助成 

    中島史恵

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    Authorship:Principal investigator  Grant type:Competitive

    Grant amount:\3000000 ( Direct Cost: \3000000 )

  2. 脂質酸化 酵素の協調的作用により生成される新奇生理活性脂質の解析

    2023.4 - 2024.3

    天野エンザイム酵素研究助成 

    中島史恵

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    Authorship:Principal investigator  Grant type:Competitive

    Grant amount:\600000 ( Direct Cost: \600000 )

KAKENHI (Grants-in-Aid for Scientific Research) 6

  1. クルクミン酸化物による炎症抑制機構の解明

    Grant number:25K18193  2025.4 - 2027.3

    日本学術振興会  科学研究費助成事業  若手研究

    中島 史恵

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    Authorship:Principal investigator 

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

    クルクミンはウコンに含まれるポリフェノールで、様々な健康の維持増進作用を有することが報告されている。しかし一方で、動物実験やヒト試験で同様の効果があったという報告、なかったという報告の両方があり、in vitro試験で認められた作用をin vivo試験で裏付けるほどの効果を証明するに至っていない。本研究は「生理条件下で生成されるクルクミン酸化物が炎症抑制作用の活性本体である」という仮説を立て、これを検証することを目的とする。

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  2. トランスメタボリズムにより生成する新規生理活性脂質の探索

    Grant number:25127595  2025 - 2032

    科学技術振興機構  戦略的な研究開発の推進/創発的研究支援事業

    中島 史恵

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    生理活性脂質はヒトの健康や病気に関わる重要な分子です。本研究では、これまで別々に作用し異なる生理活性脂質の生成に関与すると考えられていた酵素が、協調的に作用する「トランスメタボリズム」という概念を着想し、これまでにない新しい生理活性脂質の創出を目指します。異なる生物種が持つ酵素の組み合わせによる有用な脂質の創出は、食品や医薬品における新たな価値を生み出し、破壊的イノベーションにつながります。

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  3. Omics of morphogenesis and physiological function in plasma treated plants focusing on their root system

    Grant number:24H02256  2024.4 - 2029.3

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

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    Authorship:Coinvestigator(s) 

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  4. 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

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    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。
    内因性あるいは外因性の分子の中には、タンパク質に対しアダクトを形成するものが報告されており、疾患状態に起因する内因性代謝物や食物由来成分の代謝物の一部が、タンパク質との反応性をもつアダクト形成物質として作用し、生体内のタンパク質に様々なアダクトを形成していることが考えられる。そこで本研究では、代謝物アダクトームの解析方法を確立し、生体の状態や疾患状態を反映する代謝物アダクトを同定することを目的としている。
    これまでに見出した、酸化リン脂質および酸化コレステロールが修飾したリジンアダクトについて、ヒト酸化LDLにおける定量解析を行なうとともに、脂質異常症モデルマウス血清タンパク質における定量解析を行なった。その結果、コントロールと比較して増加するアダクトを見出した。これらのアダクトに関してマクロファージによる貪食に影響するかを評価したところ、酸化リン脂質修飾リジンアダクトがマクロファージにより認識されていることが判明した。さらに主要な脂質アルデヒドのひとつであるアクロレインに関して、モデルアミノ酸およびモデルタンパク質と反応させた後、生成したアダクトに関して分子ネットワーク解析を実施した。その結果、関連するアダクトが同一のクラスターに位置することを確認した。またマクロファージ様細胞が放出する細胞外微粒子に含まれるタンパク質の翻訳後修飾の解析により見出したアルギニン修飾体に関して、その標的となるタンパク質を複数同定した。
    予定通り酸化修飾リジンアダクトの定量解析が進んでいる。またモデル反応において分子ネットワーク解析も完了している。
    酸化リン脂質修飾リジンアダクトに関しては、さらに定量解析を進めるとともに、マクロファージにおける認識機構の解析を行なう。また酸化リン脂質修飾の標的となるタンパク質の解析を進め、酸化リン脂質が関与する細胞応答や病態との関連性を明らかにする。細胞外小胞に含まれるアルギニン修飾体に関しては、細胞外小胞にどのように積み込まれるのかを解析する。

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  5. Arachidonic acid-derived lipid mediator hemiketal E2 induces angiogenesis through protein modification

    Grant number:23K13881  2023.4 - 2025.3

    Grants-in-Aid for Scientific Research  Grant-in-Aid for Early-Career Scientists

    Nakashima Fumie

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    Authorship:Principal investigator 

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

    This project focused on the molecular mechanisms of how HKE2 induces angiogenesis through vascular endothelial growth factor receptor 2 (VEGFR2). It is unlikely that HKE2 itself can be a ligand of VEGFR2 since all known VEGFR2 agonists are peptides. Based on this, the presence of a protein which mediates phosphorylation of VEGFR2 was speculated. HKE2 possesses α,β-unsaturated carbonyl, which shows high reactivity with thiols. Indeed, it was revealed that HKE2 modifies Cys residue of protein tyrosine phosphatase 1B (PTP1B). Furthermore, dephosphorylation activity of PTP1B decreased by the modification. These results suggested that HKE2 induces angiogenesis through VEGFR2 phosphorylation as a consequence of inhibiting PTP1B activity by Cys residue modification.

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  6. Formation of novel eicosanoids in the biosynthetic convergence of the 5-LOX and COX-2 pathways

    Grant number:22K20570  2022.8 - 2024.3

    Grants-in-Aid for Scientific Research  Grant-in-Aid for Research Activity Start-up

    Nakashima Fumie

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    Authorship:Principal investigator 

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

    This study focused on the formation of novel eicosanoid biosynthesized in the convergence of three enzymes, 5-lipoxygenase, cyclooxygenase-2, and thromboxane synthase. Using differentiated HL-60 as an in vitro model of mature granulocyte, biosynthesis of novel eicosanoid was evaluated using mass spectrometry. A novel eicosanoid 5-OH-thromboxane B2, the 5-hydroxy analog of arachidonic acid derived thromboxane B2, was formed by the stimulation of LPS and calcium ionophore.

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Teaching Experience (On-campus) 7

  1. Chemical Biology

    2024

  2. 応用生命科学科実験実習

    2024

  3. Basics of Bioagricultural Sciences

    2024

  4. Chemical Biology

    2023

  5. 応用生命科学科実験実習

    2023

  6. Chemical Biology

    2022

  7. 応用生命科学科実験実習

    2022

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Teaching Experience (Off-campus) 1

  1. 食品分析学

    2023.9 Chubu University)