Updated on 2022/03/30

写真a

 
NATORI Yujin
 
Organization
Graduate School of Medicine Center for Research of Laboratory Animals and Medical Research Engineering Division for Advanced Medical Research Assistant Professor
Graduate School
Graduate School of Medicine
Undergraduate School
School of Medicine Department of Medicine
Title
Assistant Professor
Contact information
メールアドレス

Degree 1

  1. 博士(薬学) ( 2017.10   帝京大学 ) 

Research Interests 5

  1. 脂肪細胞

  2. 分子生物学

  3. メタボローム解析

  4. メタボロミクス

  5. シアリダーゼ

Research Areas 2

  1. Life Science / Pharmaceutical hygiene and biochemistry

  2. Life Science / Pharmaceutical hygiene and biochemistry

Research History 4

  1. 名古屋大学大学院   医学系研究科   助教

    2018.9

      More details

    Country:Japan

  2. Nagoya University   Graduate School of Medicine   Assistant Professor

    2018.9

  3. Teikyo University   Faculty of Pharmaceutical Sciences   Assistant Professor

    2017.11 - 2018.8

      More details

    Country:Japan

  4. Teikyo University   Faculty of Pharma-Science   Assistant

    2011.4 - 2017.10

Committee Memberships 1

  1. 応用物理学会 教育分科会   リフレッシュ理科教室実行委員  

    2012.4 - 2018.9   

      More details

    Committee type:Academic society

 

Papers 9

  1. A simple method for the determination of glyphosate, glufosinate and their metabolites in biological specimen by liquid chromatography/tandem mass spectrometry: an application for forensic toxicology. Reviewed

    Tomomi Ohara, Takashi Yoshimoto, Yujin Natori, Akira Ishii

    Nagoya journal of medical science   Vol. 83 ( 3 ) page: 567 - 587   2021.8

     More details

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

    Glyphosate (GLYP) and glufosinate (GLUF) are phosphorus-containing amino acid type herbicides that are used worldwide. With their rising consumptions, fatal intoxication cases due to these herbicides, whether accidental or intentional, cannot be ignored. Both compounds are difficult to detect, and their pretreatment for instrumental analysis are complicated and time-consuming. Our aim was to develop a simple and rapid quantification method for the two herbicides and their metabolites with liquid chromatography/tandem mass spectrometry (LC/MS/MS). We also compared 2-amino-4-phosphonobutyric acid and DL-2-amino-5-phosphonopentanoic acid as alternative internal standards (IS) to GLYP13C2 15N. Herbicide-containing specimens were highly diluted, evaporated to dryness, and derivatized with acetate/acetic anhydride and trimethyl orthoacetate for 30 min. at 120°C. Our optimized LC conditions successfully separated the target analytes, with acceptable linearities (R 2>0.98) and matrix effects (65%-140%). Accuracy and precision ranged from 80.2 % to 111 %, and from 1.3 % to 13 % at the higher concentration, respectively.The concentration of the herbicides and their metabolites were investigated in a postmortem case of suspected herbicide poisoning cases, in which we detected GLYP and its metabolites. Using one of the three ISs, the GLYP concentrations ranged from 3.1 to 3.5 mg/mL, and 3.3 to 4.5 mg/mL in plasma and urine, respectively; GLYP metabolite concentrations in plasma and urine were 18 to 20 μg/mL and 44 to 54 μg/mL. We thus succeeded in developing a rapid method without extraction for measuring GLYP and GLUF along with their metabolites, and demonstrated its practical applicability.

    DOI: 10.18999/nagjms.83.3.567

    Web of Science

    Scopus

    PubMed

  2. Triiodothyronine Aggravates Global Cerebral Ishemia-Reperfusion Injury in Mice Reviewed

    Masaru Doshi, Shiro Watanabe, Yujin Natori, Makoto Hosoyamada, and Yutaka Hirashima-Akae

    Biological and Pharmaceutical Bulletin   Vol. 44 ( 12 ) page: 1823 - 1831   2021.12

     More details

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

    DOI: https://doi.org/10.1248/bpb.b21-00424

  3. A simple method for the determination of glyphosate, glufosinate and their metabolites in biological specimen by liquid chromatography- tandem mass spectrometry (LC-MS/MS): An application for forensic toxicology Reviewed

    Tomomi Ohara, Takashi Yoshimoto, Yujin Natori and Akira Ishii

    Nagoya Journal of Medical Science   Vol. 83 ( 3 )   2021.8

     More details

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

  4. Triiodothyronine Aggravates Global Cerebral Ischemia–Reperfusion Injury in Mice Reviewed

    Masaru Doshi, Shiro Watanabe, Yujin Natori, Makoto Hosoyamada, Yutaka Hirashima-Akae

    Biological and Pharmaceutical Bulletin   Vol. 44 ( 12 ) page: 1824 - 1831   2021

     More details

    Language:English   Publishing type:Research paper (scientific journal)   Publisher:Pharmaceutical Society of Japan  

    <p>Thyroid hormones (THs) have been suggested to play an important role in both physiological and pathological events in the central nervous system. Hypothyroidism, which is characterized by low levels of serum THs, has been associated with aggravation of ischemic neuronal injuries in stroke patients. We hypothesized that administration of T<sub>3</sub>, the main active form of THs, may attenuate the ischemic neuronal injuries. In mice, global cerebral ischemia (GCI), which is induced by transient occlusion of the bilateral common carotid artery, causes neuronal injuries by inducing neuronal death and activating inflammatory responses after reperfusion in the hippocampus. In this study, we examined the effect of T<sub>3</sub> administration on DNA fragmentation induced by neuronal death and the activation of inflammatory cells such as astrocytes and microglia in the hippocampus following GCI. The content of nucleosomes generated by DNA fragmentation in the hippocampus was increased by GCI and further increased by T<sub>3</sub> administration. The protein expression levels of glial fibrillary acidic protein (GFAP), an astrocytic marker, and Ionized calcium binding adaptor protein 1 (Iba1), a microglial marker, in the hippocampus were also increased by GCI and further increased by T<sub>3</sub> administration. The levels of T<sub>3</sub> in both the serum and hippocampus were elevated by T<sub>3</sub> administration. Our results indicate that T<sub>3</sub> administration aggravates GCI–reperfusion injury in mice. There may be an increased risk of aggravation of ischemic stroke by the excessive elevation of T<sub>3</sub> levels during the drug treatment of hypothyroidism.</p>

    DOI: 10.1248/bpb.b21-00424

    Web of Science

    Scopus

    PubMed

    CiNii Research

  5. 労働現場で発生したトルエン中毒による死亡の二事例

    石井 晃、名取 雄人

    産業医学ジャーナル   Vol. 43 ( 5 ) page: 32 - 35   2020.9

     More details

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

  6. Development of "Quick-DB forensic": A total workflow from QuEChERS-dSPE method to GC-MS/MS quantification of forensically relevant drugs and pesticides in whole blood. Reviewed International journal

    Maiko Kusano, Yuki Sakamoto, Yujin Natori, Haruhiko Miyagawa, Hitoshi Tsuchihashi, Akira Ishii, Kei Zaitsu

    Forensic science international   Vol. 300   page: 125 - 135   2019.7

     More details

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

    Trends in forensic toxicology show the advancement of rapid and sensitive analytical methods for qualitative and quantitative analysis of drugs of abuse. However, forensic toxicologists are continuously faced with the challenges of identifying and quantifying drug blood concentration while simultaneously struggling with manpower shortage. In view of developing a simple and productive toxicological analysis method encompassing total workflow from sample preparation to quantitative analysis, here we describe a simple, robust, and sensitive method for the simultaneous determination and quantification of 63 forensically relevant drugs and pesticides in human whole blood. The method is based on sample preparation by a modified QuEChERS extraction and dispersive solid-phase extraction (dSPE) clean-up followed by gas chromatography-tandem mass spectrometry (GC-MS/MS) analysis. Limits of detection of the target analytes in whole blood ranged in the few ng/mL-order levels. Intra- and inter-day validation result ranges were 0-24% for accuracy (% error) and 0.8-26% for precision (%RSD). Recovery rates ranged from 66% to 84% for barbiturates, 36% to 110% for benzodiazepines, 41% to 86% for tri/tetracyclic antidepressants, 15% to 81% for drugs of abuse, 28% to 44% for phenethylamines, and 25% to 118% for pesticides. The validated results were used to develop a user-friendly, systematic, and quantitative toxicological GC/MS/MS system and software "Quick-DB Forensic".

    DOI: 10.1016/j.forsciint.2019.03.048

    Web of Science

    Scopus

    PubMed

  7. NEU1 sialidase controls gene expression and secretion of IL-6 and MCP-1 through NF-κB pathway in 3T3-L1 adipocytes. Reviewed International journal

    Yujin Natori, Miwako Nasui, Kiyoto Edo, Shogo Sato, Takuya Sakurai, Takako Kizaki, Fumiko Kihara-Negishi

    Journal of biochemistry   Vol. 162 ( 2 ) page: 137 - 143   2017.8

     More details

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

    A sialidase NEU1 that removes sialic acids from glycoconjugates has been implicated in diverse cellular functions. Aberrant NEU1 activity is associated with various pathologies including lysosomal storage disorder sialidosis, autoimmune diseases and the malignancy and metastasis of cancer cells. We recently reported that NEU1 activity increases during 3T3-L1 adipogenesis and that it is higher in the epididymal fat of obese and diabetic mice. However, the precise functions of NEU1 in adipocytes have not been elucidated. Knockdown of NEU1 using siRNA transfection in 3T3-L1 adipocytes significantly decreased the mRNA expression and protein secretion of IL-6 and MCP-1 induced by LPS. The promoter activities of both IL-6 and MCP-1 as well as nuclear factor-kappa B (NF-κB) nuclear translocation were reduced in adipocytes transfected with an siRNA sequence that targets NEU1(siNEU1). NEU1 suppression using siNEU1 affected TLR4 sialylation. These findings suggest that NEU1 is involved in the production of IL-6 and MCP-1 in adipocytes possibly through TLR4/NF-κB signalling.

    DOI: 10.1093/jb/mvx006

    PubMed

  8. Neu1 sialidase interacts with perilipin 1 on lipid droplets and inhibits lipolysis in 3T3-L1 adipocytes. Reviewed International journal

    Yujin Natori, Miwako Nasui, Fumiko Kihara-Negishi

    Genes to cells : devoted to molecular & cellular mechanisms   Vol. 22 ( 5 ) page: 485 - 492   2017.5

     More details

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

    Fatty acids are stored within adipocytes in lipid droplets (LDs) as triacylglycerol (TG), which is converted to free fatty acid (FFA) and glycerol via lipolysis. Increased plasma FFA levels in obesity are associated with several clinical conditions. We previously found that Neu1 activity is aberrant in the epididymal fat and liver of obese and diabetic mice. Here, we examined involvement of Neu1 in lipolysis in 3T3-L1 adipocytes. Small interfering RNA against Neu1 was introduced into adipocytes, and glycerol concentrations were measured in the culture medium. We then assessed the effects of Neu1 knockdown on lipolytic protein expression and phosphorylation, as well as interactions between perilipin 1 (Plin1) and hormone-sensitive lipase (HSL) after isoproterenol (IS) stimulation. Interactions between Neu1 and Plin1 were analyzed by immunoprecipitation and immunofluorescent imaging using adipocytes transfected with pCMV6-mNeu1-myc-DYKDDDDK (mNeu1DDK). Neu1 knockdown increased glycerol concentrations in culture media and Plin1 phosphorylation in whole lysates of IS-stimulated cells. Neu1 knockdown increased interaction between Plin1 and HSL after IS stimulation whereas that between Neu1 and Plin1 on LD observed under basal conditions was lost. These results suggest that Neu1 inhibits lipolysis induced by β-adrenergic stimulation in adipocytes via interactions with Plin1 on LD.

    DOI: 10.1111/gtc.12490

    PubMed

  9. Acidic sialidase activity is aberrant in obese and diabetic mice. Reviewed

    Yujin Natori, Naoki Ohkura, Miwako Nasui, Gen-ichi Atsumi, Fumiko Kihara-Negishi

    Biological & pharmaceutical bulletin   Vol. 36 ( 6 ) page: 1027 - 31   2013

     More details

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

    Mammalian sialidases (NEU1, NEU2, NEU3 and NEU4) that remove sialic acids from glycoconjugates have been implicated in diverse cellular functions. Human sialidases are involved in the development of various disease states such as cancer, diabetes and arteriosclerosis. Unregulated acidic sialidase NEU1 activity is associated with the pathogenesis of lysosomal storage disorder (LSD) sialidosis, abnormal immune responses and cancer progression. Obesity is closely related to several chronic diseases such as diabetes, cardiovascular diseases, hyperlipidemia or hypertension that are associated with metabolic syndrome. We examined fluctuations in mRNA levels and sialidase activities of NEU1 in two strains of obese and diabetic mice to assess the involvement of NEU1 in obesity. The activity of NEU1 was preferentially higher in epididymal fat and lower in the livers of two strains of obese and diabetic mice. Fluctuations in NEU1 activity might be associated with the pathological status of these tissues in obesity.

    DOI: 10.1248/bpb.b12-00995

    PubMed

▼display all

KAKENHI (Grants-in-Aid for Scientific Research) 4

  1. Elucidation of acute poisoning mechanism due to abuse of CB1 receptor agonist.

    Grant number:21K17323  2021.4 - 2023.3

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research Grant-in-Aid for Early-Career Scientists  Grant-in-Aid for Early-Career Scientists

      More details

    Authorship:Principal investigator 

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

  2. 分解後プロテオミクス:法医学からの新規プロテオミクス

    Grant number:19K22756  2019.6 - 2022.3

    日本学術振興会  科学研究費助成事業 挑戦的研究(萌芽)  挑戦的研究(萌芽)

    石井 晃, 名取 雄人, 名取 雄人

      More details

    Authorship:Coinvestigator(s) 

    本研究では、質量分析法を用いたペプチド解析を行うことにより、最初はトリプシン消化フラグメントを用いて、従来の法医生化学検査では測定不能であった試料における目的タンパクを定量し、次いで、実検体で切断されているペプチドフラグメントを同定し、法医診断に資するタンパク(ペプチド)マーカーの探索を行うことを目的とする。対象となるタンパクとしては、熱中症で上昇するミオグロビン、心不全で上昇するNT-proBNPが挙げられる。
    最初の目標は尿中ミオグロビンであり、現在、標準品ヒトミオグロビンのトリプシン消化フラグメントの解析を行うことにより、実験条件の検討を行っている。トリプシン消化により、ヒトミオグロビンは19のフラグメントに分解し、それぞれについて、MS/MS上でのトランジションの最適化を行った。次いで、これらフラグメントをセミミクロカラム及びミクロカラムで分離し、分離性能及び感度を比較した。セミミクロカラムによる分離と比較すると、ミクロカラムによる分離を行うことにより、分離時間は30分から10分と短縮でき、面積値で1.5倍から9倍程度の感度の上昇が認められ、ミクロカラムがこれらフラグメントの検出に有用であることが示された。現在、標準尿に標準ミオグロビンを添加したものを室温で放置し、その後トリプシン消化を行い、ペプチドの絶対強度を比較した。すると、ペプチド間で強度に差が見られ、定量に適したペプチドが選択できる可能性が示唆された。また、同時にSDS-PAGEによるミオグロビンの分離を行い、分解速度検討のための基礎データを採取している。

  3. 危険ドラッグとして乱用されるCB1受容体アゴニストのミトコンドリア障害機序の解明

    Grant number:19K19485  2019.4 - 2021.3

    日本学術振興会  科学研究費助成事業 若手研究  若手研究

    名取 雄人

      More details

    Authorship:Principal investigator 

    Grant amount:\4160000 ( Direct Cost: \3200000 、 Indirect Cost:\960000 )

    近年、危険ドラッグの乱用が中毒死を含めた健康被害や異常行動などを引き起こし、社会的な問題となっている。このような危険ドラッグのなかでも、テトラヒドロカンナビノール(THC)と同様の作用を持つ合成カンナビノイド類は、THCや内在性リガンドと同様にカンナビノイド受容体CB1およびCB2と結合して、その活性を現す。CB1受容体は、中枢神経系において発現が高く、細胞膜とミトコンドリア外膜に存在するとされている。特に海馬では、シナプス前終末のCB1受容体の活性化がグルタミン酸の放出抑制を介して逆行性シナプス伝達抑制に関与する。
    神経細胞モデルとして汎用されるマウスNeuroblastoma由来であるNeuro2Aはレチノイン酸刺激により神経細胞分化によってNeuriteを形成するが、合成カンナビノイドであるHU-210 によっても同様にNeuriteを形成する。合成カンナビノイドは一般にカンナビノイド受容体を刺激することでその作用を示すが、危険ドラッグとして規制から逃れるためにその構造に多くの修飾が加えられているため、その作用機序にはこれまでに知られていないメカニズムが存在する可能性がある。そこで本年度はNeuro2A細胞を用いて、カンナビノイド受容体アゴニストであるAM-2201 やHU-210がNeuro2A の分化に及ぼす機序の違いを調べるための予備検討を行った。Neuro2Aは先に述べたようにレチノイン酸によってもNeurite形成を示すが、培養液中の血清濃度の違いによって、レチノイン酸がNeurite形成に及ぼす影響が異なることが知られている。そこで、予備検討として、Neuro2Aの培養液中血清を変動させたところ、CB1 受容体の発現が変動した。このことから、培養液中の血清濃度によってカンナビノイド受容体アゴニストの作用に変動が生じることが考えられた。

  4. Accurate measurement of natural toxins in body fluids using deuterated standards and search of specific markers for the rapid diagnosis

    Grant number:18H03064  2018.4 - 2021.3

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

      More details

    Authorship:Coinvestigator(s) 

 

Teaching Experience (On-campus) 4

  1. ベーシックトレーニング(薬毒物分析)

    2020

  2. 社会医学実習

    2020

  3. 社会医学実習

    2019

  4. 医学入門

    2019