Updated on 2024/11/15

写真a

 
Nakagawa Hiroshi
 
Organization
Graduate School of Veterinary Science Department of Veterinary Science Lecturer
School of Veterinary Science Department of Veterinary Science
Title
Lecturer
Affiliation
Institute of Veterinary Science
Affiliation campus
Rinku Campus

Position

  • Graduate School of Veterinary Science Department of Veterinary Science 

    Lecturer  2022.04 - Now

  • School of Veterinary Science Department of Veterinary Science 

    Lecturer  2022.04 - Now

Degree

  • 博士（獣医学） （ Others ） (   Osaka prefecture univercity )

Research Areas

  • Life Science / Veterinary medical science  / Applied Veternary Science

  • Life Science / Veterinary medical science

Research Interests

  • 毒性学

  • Toxicology

Research subject summary

  • 細胞内に取り込まれたマイクロプラスチックの毒性評価

  • フッ素の細胞毒性機序について

  • ERストレス由来アポトーシスの実行メカニズムについて

  • 細胞内小胞輸送制御メカニズムについて

Research Career

  • Regulation of intracellular vesicle transport

    intracellular traffic, cell death, cytotoxicity, trimeric G protein, kinase signalling  Individual

    2001 - 2016 

  • Fluoride toxicity

    fluoride, cytotoxicity, intracellular traffic, cell death, ER stress  Individual

    2001 - 2016 

  • Mechanism of ER stress-mediated apoptosis

    apoptosis, ER stress, cytotoxicity, caspase  Individual

    2001 - 2016 

Professional Memberships

  • The Japanese Pharmacological Society

    2002.04 - Now   Domestic

  • The Japanese Society of Veterinary Science

    1999.04 - Now   Domestic

  • The Japanese Society of Toxicology

    1997.04 - Now   Domestic

  • 日本薬理学会

  • 日本獣医学会

  • 日本トキシコロジー学会

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Committee Memberships (off-campus)

  • 平成23年食品衛生管理者の登録講習会実習講師   日本食品添加物協会  

    2011.04 - 2012.03 

Job Career (off-campus)

  • Osaka Metropolitan University   Laboratory of Toxicology, Graduate school of Veterinay Science   Junior Associate Professor

    2022.04 - Now

  • Osaka Prefecture University   junior associate professor

    2021.09 - 2022.03

  • - 大阪府立大学大学院生命環境科学研究科   助教

    2007 - 2021.08

  • Agriculture and Biological Sciences,

  • Osaka Prefecture University

Papers

  • Effect of long-term inorganic arsenic exposure on erythropoietin production in vitro

    Haque M.A.

    Toxicology in Vitro   99   105877   2024.08（ ISSN:08872333 ）

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  • Effect of long-term treatment with trivalent chromium on erythropoietin production in HepG2 cells

    Nishimura K.

    Archives of Biochemistry and Biophysics   752   109872   2024.02（ ISSN:00039861 ）

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  • Effect of long-term treatment with metal compounds on itch mediator production in keratinocytes

    NISHIMURA Kazuhiko, MIZUKAWA Yuka, HAQUE Md. Anamul, NAKAGAWA Hiroshi

    Annual Meeting of the Japanese Society of Toxicology   51.1 ( 0 )   P-142   2024

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    <p>Keratinocytes are important in the protective barrier of the epidermis and release cytokines, including itch mediators, in response to external stimuli. Itching may occur when various chemical substances, including cosmetics, are applied to the skin, but the cause and mechanism of its occurrence have not been fully elucidated. In this study, we analyzed whether the long-term effects of metal compounds contained in cosmetics on keratinocytes affect the production of itch mediators by keratinocytes due to external stimuli. Human keratinocyte PHK16-0b cells, which have been subcultured for over 3 weeks in MCDB153 medium treated with aluminum chloride (Al) and cobalt chloride (Co), were cultured for 24 hours with histamine, lipopolysaccharide (LPS), and Phorbol12-myristate13-acetate (PMA). The mRNA expression levels of itch mediators interleukin (IL)-31, -33, thymic stromal lymphopoietin (TSLP), Cathepsin S, and Endothelin-1 were measured using real-time PCR. Long-term Al treatment increased mRNA expression of itch mediators, whereas Co treatment decreased them. The protein levels of IL-33 and TSLP, which are mainly produced by keratinocytes, showed changes similar to mRNA expression. In long-term Al treatment, the addition of PMA increased the mRNA expression level of itch mediators. In long-term treatment with Co, the suppression by Co was canceled by the addition of histamine, LPS, and PMA. These results suggested that the increase in itch mediator mRNA expression caused by histamine, LPS, and PMA stimulation in keratinocytes was affected by long-term treatment of Al and Co.</p>

    DOI： 10.14869/toxpt.51.1.0_p-142

  • The impact of long-term exposure to low levels of arsenate on erythropoietin production in vitro and in vivo

    HAQUE Md. Anamul, NAKAGAWA Hiroshi, NISHIMURA Kazuhiko

    Annual Meeting of the Japanese Society of Toxicology   51.1 ( 0 )   P-14S   2024

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    <p>Long-term exposure to inorganic arsenic causes not only skin symptoms but also various toxicities, such as anemia. However, the impacts of low levels of inorganic arsenic have not yet been elucidated. We reported that exposure to low levels of arsenate, a pentavalent arsenic, affected the production of erythropoietin (EPO) in HepG2 cells. This study investigates the impact of low-level long-term arsenate exposure on EPO production both in vitro and in vivo. In vitro experiments involved subculturing HepG2 cells for three weeks and treating them with arsenate at levels ranging from 1–10 µM. Compared to untreated cells, EPO production and responsiveness to EPO production stimuli were reduced. In the in vivo experiments, mice were exposed to arsenate at a dose of 60 nmol of arsenate per day for two months. Compared to untreated mice, treated mice showed decreased EPO mRNA levels, although there were no differences in body weight or hematocrit. The stimulating impact of EPO production on liver and kidney cortical cells recovered from mice was significantly reduced in arsenate-treated mice. In HepG2 cells treated with arsenate, while ROS production increased, the response to remove oxidative stress was also enhanced, suggesting that the promotion of EPO production by ROS production was attenuated. There is a possibility that long-term low-level arsenate exposure may not generally be harmful, but it might cause anemia and other health problems by preventing the body from producing enough EPO.</p>

    DOI： 10.14869/toxpt.51.1.0_p-14s

  • Examination of the involvement of tight junctions in the permeation of polystyrene particles in a Caco-2 cell intestinal epithelial model

    NAKAGAWA Hiroshi, OKAWA Chiaki, HAQUE Md. Anamul, NISHIMURA Kazuhiko

    Annual Meeting of the Japanese Society of Toxicology   51.1 ( 0 )   P-145   2024

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    <p>It has been reported that when relatively large polystyrene particles (PPs) with a diameter of approximately 0.1 µm, which are included in the category of microplastics, are orally administered to mice, they pass through the intestinal epithelium and reach internal organs. We have previously demonstrated that PPs with a diameter of 0.1 µm are taken up by cells in a Caco-2 cell intestinal epithelial model, and some of them are taken up into lysosomes, which modulates the localization of tight junction (TJ) proteins. In this study, we focused on the mTOR signal as a candidate signal factor that modulates TJ, which can originate from the lysosome, and evaluated the influence of PPs. Furthermore, we investigated whether a paracellular transport pathway involving TJs through the intercellular space is involved in the permeation of PPs in an intestinal epithelial model.</p><p>PPs accumulated in lysosomes, which decreased mTOR activity and modulated the localization of TJ proteins, resulting in a decrease in TEER. On the other hand, PPs penetrated the intestinal epithelial model, although no effect of polystyrene particle treatment on paracellular transport was observed. Therefore, it was considered that the majority of the penetration of PPs through the intestinal epithelium depends on transcytosis rather than intercellular spaces. Furthermore, although there was no relation to the permeation of PPs, modulation of TJ is expected to affect the permeability of other factors such as viruses.</p>

    DOI： 10.14869/toxpt.51.1.0_p-145

  • Effect of pentavalent inorganic arsenic salt on erythropoietin production and autophagy induction

    Nishimura K.

    Archives of Biochemistry and Biophysics   734   109487   2023.01（ ISSN:00039861 ）

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  • Effect of trivalent chromium on erythropoietin production and the prevention of insulin resistance in HepG2 cells

    Kazuhiko Nishimura, Suzuka Iitaka, Hiroshi Nakagawa

    Archives of Biochemistry and Biophysics   708   108960 - 108960   2021.09（ ISSN:0003-9861 ）

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    Publishing type：Research paper (scientific journal)  

    DOI： 10.1016/j.abb.2021.108960

  • Carbon tetrachloride suppresses ER‐Golgi transport by inhibiting COPII vesicle formation on the ER membrane in the RLC‐16 hepatocyte cell line

    Hiroshi Nakagawa, Masayuki Komori, Kazuhiko Nishimura

    Cell Biology International   45 ( 3 )   633 - 641   2021.03（ ISSN:1065-6995 ） （ eISSN:1095-8355 ）

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    Publishing type：Research paper (scientific journal)  

    DOI： 10.1002/cbin.11510

    Other URL： https://onlinelibrary.wiley.com/doi/full-xml/10.1002/cbin.11510

  • Effects of sorbitol and lactate on erythropoietin production in HepG2 cells.

    Kazuhiko Nishimura, Hideaki Katsuyama, Masahiro Ohishi, Arisa Hirabayashi, Kensyo Matsuda, Hiroshi Nakagawa

    Biochemical and biophysical research communications   523 ( 1 )   54 - 59   2020.02

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    Publishing type：Research paper (scientific journal)   International / domestic magazine：International journal  

    Promotion of erythropoietin (EPO) production is important for erythropoiesis as well as cell viability. The most effective inducing factor for EPO production is hypoxia. Hypoxia inducible factor (HIF), a regulator of EPO production, is increased under hypoxic conditions and is also affected by various regulators such as sirtuin1 (SIRT1). SIRT1 is regulated by the cytoplasmic redox state, which is thought to affect EPO production. Therefore, we investigated the effects of sorbitol and lactic acid, which serve as substrates for cellular respiration and bring cells into a reduced state, on EPO production in HepG2 cells. The addition of low-concentration sorbitol to HepG2 cells produced a mildly reduced state similar to that of hypoxia and increased NAD+, SIRT1, and HIF-α, and EPO mRNA expression. On the other hand, lactate suppressed EPO mRNA expression at all concentrations. Inhibition of lactate production from pyruvate abolished the effect of low sorbitol concentrations on EPO mRNA expression. When low-concentration sorbitol and a reducing agent were administered simultaneously, the effect of increasing EPO mRNA expression disappeared. It was suggested that SIRT1 and EPO production increased under conditions where lactate production was not suppressed, even under mildly reduced conditions similar to hypoxia.

    DOI： 10.1016/j.bbrc.2019.12.001

    PubMed

  • The effect of hemin-induced oxidative stress on erythropoietin production in HepG2 cells. Reviewed

    Nishimura K, Tokida M, Katsuyama H, Nakagawa H, Matsuo S.

    Cell Biol Int. 雑誌 Wiley   38   1321 - 1329   2014

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    Kind of work：Joint Work  

  • Selection of autophagy or apoptosis in cells exposed to ER-stress depends on ATF4 expression pattern with or without CHOP expression. Reviewed

    Matsumoto H, Miyazaki S, Matsuyama S, Takeda M, Kawano M, Nakagawa H, Nishimura K, Matsuo S

    Bio Open 雑誌 The Company of Biologists Ltd   2 ( 10 )   1084 - 1090   2013.10

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    Kind of work：Joint Work  

  • Sar1 translocation onto the ER membrane for vesicle budding has different pathways for promotion and suppression of ER-to-Golgi transport mediated through H89-sensitive kinase and ER-resident G protein. Reviewed

    Nakagawa H, Ishizaki M, Miyazaki S, Abe T, Nishimura K, Komori M, Matsuo S

    Mol Cell Biochem 雑誌 Springer   366 ( 41641 )   175 - 182   2012.07

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    Kind of work：Joint Work  

  • ER-Resident Gi2 Protein Controls Sar1 Translocation onto the ER During Budding of Transport Vesicles. Reviewed

    Nakagawa H, Umadome H, Miyazaki S, Tanaka K, Nishimura K, Komori M, Matsuo S

    J Cell Biochem. 雑誌 Wiley   112 ( 9 )   2250 - 2256   2011.09

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    Kind of work：Joint Work  

  • H89 sensitive kinase regulates the translocation of Sar1 onto the ER membrane through phosphorylation of ER-coupled beta-tubulin. Reviewed

    Nakagawa H, Miyazaki S, Abe T, Umadome H, Tanaka K, Nishimura K, Komori M, Matsuo S

    Int J Biochem Cell Biol. 雑誌 Elsevier   43 ( 3 )   423 - 430   2011.03

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    Kind of work：Joint Work  

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Books and Other Publications

  • 薬理学・毒性学実験 第4版

    （腎毒性、環境毒性）

    文英堂出版  2023.03  （ ISBN:978-4-8300-3286-8 ）

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    Total pages：225   Responsible for pages：9   Book type：Textbook, survey, introduction

  • 獣医毒性学　第2版

    比較薬理学・毒性学会　編（ Role： Joint author）

    文永堂出版  2020.04 

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    Responsible for pages：8-15  

  • 薬理学・毒性学実験

    比較薬理学・毒性学会　編（ Role： Joint author）

    文永堂出版  2008.04 

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    Responsible for pages：159-163, 190-192  

Presentations

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Outline of collaborative research (seeds)

  • 細胞内に取り込まれたマイクロプラスチックの毒性評価

    　More details

    直径0.1µm程度のポリスチレン粒子は腸管細胞内に取り込まれ、いくつかのオルガネラ内に局在することがわかってきた。その中でもリソソームに注目し、プラスチック粒子が滞留したリソソームの機能障害をどのように・どの程度引き起こすのかを明らかにすることにより、マイクロプラスチックの細胞毒性発現の危険性の評価を行っている。

  • 細胞内小胞輸送をターゲットとする高脂血症薬の開発

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    ER-Golgi間小胞輸送において脂質もPCTV小胞にて輸送されているが、通常のタンパク輸送であるCOPII小胞輸送に比べて、輸送阻害刺激に対する感受性が高いという特徴がある。よってPCTV小胞のER-Golgi間輸送の阻害は今までにない高脂血症薬のターゲットとして有用である。

  • ERストレス由来アポトーシスの実行メカニズムの解明

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    ERストレス由来アポトーシスは、アルツハイマー病に代表される神経細胞障害病変の研究において重要であり、その細胞死実行機序について研究の過程で、ERストレスインデューサーの種類により、アポトーシス実行因子caspase-3の活性化経路が異なることを見つけている。さらに各経路の詳細な評価を行うことにより細胞死実行メカニズム解明が進み治療薬の開発に役立つと考えられる。

  • 細胞障害を惹起する細胞内小胞輸送阻害メカニズムの解明

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    細胞内小胞輸送の阻害は細胞毒性となり臓器障害を惹起する。そこでrERやgolgi等の細胞内膜系における輸送メカニズムに働く制御シグナルの解明を行っている中で細胞内膜系局在三量体Gタンパクの活性化が輸送阻害を起こし、細胞死を惹起することを明らかにしている。更なるシグナル伝達メカニズムの解析をおこなうことにより有効な治療薬の開発に役立つと考えられる。

Grant-in-Aid for Scientific Research

  • 細胞内に取り込まれた微小プラスチック粒子のリソソーム機能への影響

    Grant-in-Aid for Scientific Research(C)  2023

  • 細胞内に取り込まれた微小プラスチック粒子のリソソーム機能への影響

    Grant-in-Aid for Scientific Research(C)  2022

  • 細胞内に取り込まれた微小プラスチック粒子のリソソーム機能への影響

    Grant-in-Aid for Scientific Research(C)  2021

  • ERストレスにおけるタンパク輸送抑制へのrER膜局在三量体Gタンパクの関与

    Grant-in-Aid for Scientific Research(C)  2016

  • ERストレスにおけるタンパク輸送抑制へのrER膜局在三量体Gタンパクの関与

    Grant-in-Aid for Scientific Research(C)  2015

  • ERストレスにおけるタンパク輸送抑制へのrER膜局在三量体Gタンパクの関与

    Grant-in-Aid for Scientific Research(C)  2014

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Outline of education staff

  • 獣医学教育の応用分野に含まれる、毒性学および毒性学実習を担当する。

Charge of on-campus class subject

  • 小動物基礎臨床実習

    2024   Intensive lecture   Undergraduate

  • 毒性学実習

    2024   Weekly class   Undergraduate

  • 獣医環境科学実習

    2024   Intensive lecture   Undergraduate

  • 食品循環科学

    2024   Weekly class   Undergraduate

  • 獣医科学英語演習

    2024   Intensive lecture   Undergraduate

  • 毒性学A

    2024   Weekly class   Undergraduate

  • 毒性学基礎実習

    2024   Intensive lecture   Undergraduate

  • 獣医科学特別研究1

    2023   Intensive lecture   Graduate school

  • 生物学実験

    2023   Intensive lecture   Graduate school

  • 獣医科学特別研究1

    2023   Intensive lecture   Graduate school

  • 獣医科学特別演習1

    2023   Intensive lecture   Graduate school

  • 獣医科学ミニレビュー

    2023   Intensive lecture   Graduate school

  • 毒性学

    2023   Weekly class   Undergraduate

  • 獣医体験演習

    2023   Weekly class   Undergraduate

  • 毒性学B

    2023   Weekly class   Undergraduate

  • 毒性病理学実習

    2023   Intensive lecture   Undergraduate

  • 毒性学実習

    2023   Weekly class   Undergraduate

  • Practice in Basic Toxicology

    2021   Practical Training  

  • Practice in Veterinary Environmental Science

    2021   Practical Training  

  • Practice in Toxicologic Pathology

    2021   Practical Training  

  • Practice in Toxicology

    2021   Practical Training  

  • Fundamental Experiments of Biology

    2021   Practical Training  

  • Basic clinical practices

    2021   Practical Training  

  • Global Circulation of Food and Hazards in Environments

    2021    

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Faculty development activities

  • feedbackstudio_WEBclicker説明会参加  2022

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    feedbackstudio_WEBclickerの説明会へのonkine参加

  • FD対応資料の作製保存  2022

  • FD対応資料の作製保存  2021

Number of instructed thesis, researches

  • 2022

    Number of instructed the graduation thesis：3  Number of graduation thesis reviews：2

Visiting Lectures　⇒ Link to the list of Visiting Lectures

  • 細胞内輸送機構と細胞死の制御

    Category：Agricultural science (applied biology, biofunctional chemistry, green space environmental science),　Veterinary

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    Audience：High school students,　College students,　Teachers,　Researchers,　General,　Company,　Civic organization

    Keyword：ERストレス由来アポトーシス 

    細胞内輸送機構と細胞死誘導機構の関連について

Academic Activities

  • BMC Gastroenterology

    Role(s)： Peer review

    2023.01 - Now

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    Type：Peer review 

  • BMC Gastroenterology

    Role(s)： Peer review

    2022.09 - 2023.02

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    Type：Peer review 

Foreigner acceptance

  • 2023

    International Students :1

  • 2022

    International Students :1

  • 2021

    International Students :1