Suematsu, Makoto

写真a

Affiliation

School of Medicine, Department of Biochemistry (Shinanomachi)

Position

Professor

External Links

 

Papers 【 Display / hide

  • 2-Nitroimidazoles induce mitochondrial stress and ferroptosis in glioma stem cells residing in a hypoxic niche

    Koike N., Kota R., Naito Y., Hayakawa N., Matsuura T., Hishiki T., Onishi N., Fukada J., Suematsu M., Shigematsu N., Saya H., Sampetrean O.

    Communications Biology (Communications Biology)  3 ( 1 ) 450 2020.12

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    © 2020, The Author(s). Under hypoxic conditions, nitroimidazoles can replace oxygen as electron acceptors, thereby enhancing the effects of radiation on malignant cells. These compounds also accumulate in hypoxic cells, where they can act as cytotoxins or imaging agents. However, whether these effects apply to cancer stem cells has not been sufficiently explored. Here we show that the 2-nitroimidazole doranidazole potentiates radiation-induced DNA damage in hypoxic glioma stem cells (GSCs) and confers a significant survival benefit in mice harboring GSC-derived tumors in radiotherapy settings. Furthermore, doranidazole and misonidazole, but not metronidazole, manifested radiation-independent cytotoxicity for hypoxic GSCs that was mediated by ferroptosis induced partially through blockade of mitochondrial complexes I and II and resultant metabolic alterations in oxidative stress responses. Doranidazole also limited the growth of GSC-derived subcutaneous tumors and that of tumors in orthotopic brain slices. Our results thus reveal the theranostic potential of 2-nitroimidazoles as ferroptosis inducers that enable targeting GSCs in their hypoxic niche.

  • Progesterone receptor membrane associated component 1 enhances obesity progression in mice by facilitating lipid accumulation in adipocytes

    Furuhata R., Kabe Y., Kanai A., Sugiura Y., Tsugawa H., Sugiyama E., Hirai M., Yamamoto T., Koike I., Yoshikawa N., Tanaka H., Koseki M., Nakae J., Matsumoto M., Nakamura M., Suematsu M.

    Communications Biology (Communications Biology)  3 ( 1 ) 479 2020.12

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    © 2020, The Author(s). Progesterone receptor membrane associated component 1 (PGRMC1) exhibits haem-dependent dimerization on cell membrane and binds to EGF receptor and cytochromes P450 to regulate cancer proliferation and chemoresistance. However, its physiological functions remain unknown. Herein, we demonstrate that PGRMC1 is required for adipogenesis, and its expression is significantly enhanced by insulin or thiazolidine, an agonist for PPARγ. The haem-dimerized PGRMC1 interacts with low-density lipoprotein receptors (VLDL-R and LDL-R) or GLUT4 to regulate their translocation to the plasma membrane, facilitating lipid uptake and accumulation, and de-novo fatty acid synthesis in adipocytes. These events are cancelled by CO through interfering with PGRMC1 dimerization. PGRMC1 expression in mouse adipose tissues is enhanced during obesity induced by a high fat diet. Furthermore, adipose tissue-specific PGRMC1 knockout in mice dramatically suppressed high-fat-diet induced adipocyte hypertrophy. Our results indicate a pivotal role of PGRMC1 in developing obesity through its metabolic regulation of lipids and carbohydrates in adipocytes.

  • Annexin A1 accounts for an anti-inflammatory binding target of sesamin metabolites

    Kabe Y., Takemoto D., Kanai A., Hirai M., Ono Y., Akazawa S., Horikawa M., Kitagawa Y., Handa H., Rogi T., Shibata H., Suematsu M.

    npj Science of Food (npj Science of Food)  4 ( 1 ) 4 2020.12

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    © 2020, The Author(s). Sesamin [(7α,7′α,8α,8′α)-3,4:3′,4′-bis(methylenedioxy)-7,9′:7′,9-diepoxylignane] is a major lignan in sesame seeds. Sesamin is converted to the catechol metabolite, SC1 [(7α,7′α,8α,8′α)-3′,4′-methylenedioxy-7,9′:7′,9-diepoxylignane-3,4-diol] with anti-inflammatory effects after oral administration. However, its molecular target remains unknown. Analysis using high-performance affinity nanobeads led to the identification of annexin A1 (ANX A1) as an SC1-binding protein. SC1 was found to bind to the annexin repeat 3 region of ANX A1 with a high-affinity constant (Kd = 2.77 μmol L−1). In U937 cells, SC1 exhibited an anti-inflammatory effect dependent on ANX A1. Furthermore, administration of sesamin or SC1 attenuated carbon tetrachloride-induced liver damage in mice and concurrently suppressed inflammatory responses dependent on ANX A1. The mechanism involved SC1-induced ANX A1 phosphorylation at serine 27 that facilitates extracellular ANX A1 release. Consequently, the ANX A1 released into the extracellular space suppressed the production of tumor necrosis factor α. This study demonstrates that ANX A1 acts as a pivotal target of sesamin metabolites to attenuate inflammatory responses.

  • Identification and local manipulation of bone marrow vasculature during intravital imaging

    Morikawa T., Tamaki S., Fujita S., Suematsu M., Takubo K.

    Scientific Reports (Scientific Reports)  10 ( 1 ) 6422 2020.12

    ISSN  2045-2322

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    © 2020, The Author(s). Physiological regulation of blood flow in bone marrow is important to maintain oxygen and glucose supplies but also the physiological hypoxic state of the hematopoietic stem cell (HSC) niche. However, regulatory mechanisms underlying microcirculation in the bone marrow (BM) niche remain unclear. Here, we identify vessels functioning in control of blood flow in bone marrow and assess their contractility. To evaluate contractile potential of Alexa Fluor 633 (AF633; an arterial marker)-positive vessels, we performed immunohistochemistry for α-smooth muscle actin (α-SMA) and found it expressed around AF633+ vessels in the femoral and calvarial marrow. To validate AF633+ vessel contractility, we developed a simple system to locally administer vasoactive agents that penetrate BM through transcalvarial vessels. After exposure of the calvarial surface to FITC-dextran (70 kDa), FITC intensity in calvarial bone marrow gradually increased. When we evaluated the effect of transcalvarial administration (TCA) of norepinephrine (NE) on vascular tone of AF633+ arteries and behavior of transplanted blood cells, NE administration decreased artery diameter and transendothelial migration of transplanted cells, suggesting that adrenergic signaling regulates the HSC niche microcirculation and blood cell migration into the BM via effects on BMarteries. We conclude that TCA is a useful tool for bone marrow research.

  • Vitamin B1 Supports the Differentiation of T Cells through TGF-β Superfamily Production in Thymic Stromal Cells

    Hirata S.i., Sawane K., Adachi J., Isoyama J., Sugiura Y., Matsunaga A., Hosomi K., Tomonaga T., Suematsu M., Nagatake T., Kunisawa J.

    iScience (iScience)  23 ( 9 ) 101426 2020.09

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    © 2020 The Authors Homeostatic generation of T cells, which occurs in the thymus, is controlled at least in part by endogenous cytokines and ligands. In addition, nutritional factors are other key regulators for the homeostasis of host immunity, but whether and how nutrition affects the homeostatic generation of thymocytes remains to be established. Here, we showed that vitamin B1 deficiency resulted in a bias toward the maturation of γδ thymocytes accompanied by decreased differentiation into double-positive thymocytes during thymic involution. These events were mediated through the increased production of TGF-β superfamily members due to the accumulation of branched-chain α-keto acids in thymic stromal cells. These findings revealed essential roles of vitamin B1 in the appropriate differentiation of T cells through the metabolism of thymic stromal cells.

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Papers, etc., Registered in KOARA 【 Display / hide

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Reviews, Commentaries, etc. 【 Display / hide

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Presentations 【 Display / hide

  • システム生物学を用いた血栓形成過程の生体内解析と抗血小板剤の評価

    SUEMATSU MAKOTO

    Fighting Vascular Events in Tokyo (東京、日本) , 2006.03, Oral Presentation(general)

  • 血小板血栓シミュレーションによる抗血小板薬の区別化予測と実証

    SUEMATSU MAKOTO

    第79回日本薬理学会年会 (横浜、日本) , 2006.03, Oral Presentation(general)

  • 脳微小循環機能のガス分子による制御機構

    SUEMATSU MAKOTO

    第31回日本脳卒中学会総会 (横浜、日本) , 2006.03, Oral Presentation(general)

  • メタボローム解析技術によるガス分子を介した細胞機能制御機構の解明と医学への応用

    SUEMATSU MAKOTO

    第28回日本分子生物学会年会 (福岡、日本) , 2005.12, Oral Presentation(general)

  • ガス分子による臓器微小循環制御機構と病態

    SUEMATSU MAKOTO

    第15回脳血管シンポジウム (大阪、日本) , 2005.09, Oral Presentation(general)

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Works 【 Display / hide

  • 学務委員会委員

    2003.10
    -
    2005.09

    Other

  • カリキュラム委員会委員

    2003.10
    -
    2005.09

    Other

  • 教育委員会委員長

    2003.10
    -
    2005.09

    Other

  • 学務委員会委員

    2001.10
    -
    2003.09

    Other

  • カリキュラム委員会委員

    2001.10
    -
    2003.09

    Other

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Awards 【 Display / hide

  • 第1回日本心脈管作働物質学会研究奨励賞

    Suematsu Makoto, 1998.07, 日本心脈管作働物質学会, 一酸化炭素による臓器微小循環機能の制御

  • 平成9年度東京生化学研究会研究助成

    Suematsu Makoto, 1997.11, 東京生化学研究会, 一酸化炭素による新しい細胞情報伝達機構の解明

  • 平成10年度日本心血管作動物質学会奨励賞

    Suematsu Makoto, 1997.07, 日本心血管作動物質学会, 一酸化炭素による肝微小循環機能の制御

 

Courses Taught 【 Display / hide

  • METABOLOMIC SYSTEMS BIOLOGY

    2021

  • MEDICAL PROFESSIONALISM 3

    2021

  • MEDICAL ENGINEERING: SEMINAR

    2021

  • MEDICAL ENGINEERING: PRACTICE

    2021

  • MEDICAL CHEMISTRY

    2021

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