• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Investigation of the involvement of oxidative stress in metabolic syndrome and the development of new anti-oxidants

Research Project

Project/Area Number 20590258
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field General pharmacology
Research InstitutionNara Medical University

Principal Investigator

YOSHIZUMI Masanori  Nara Medical University, 医学部, 教授 (60294667)

Co-Investigator(Kenkyū-buntansha) 佐藤 広康  奈良県立医科大学, 医学部, 講師 (90150309)
中山 均  奈良県立医科大学, 医学部, 講師 (50133195)
磯崎 稔  奈良県立医科大学, 医学部, 助教 (60159811)
Research Collaborator ZHAO Jing  奈良県立医科大学, 医学部, 研究生
KYOTANI Yoji  奈良県立医科大学, 医学部, 大学院生
NAKAGAWA Tokiwa  奈良県立医科大学, 医学部, 教務職員
Project Period (FY) 2008 – 2010
Project Status Completed (Fiscal Year 2010)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2010: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2009: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2008: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywordsメタボリックシンドローム / 酸化ストレス / シグナル伝達 / インスリン抵抗性 / BMK1 / 薬理学 / 抗酸化療法 / MAPキナーゼ
Research Abstract

We investigated the possible involvement of oxidative stress in metabolic syndrome using in vivo and in vitro strategies. We examined the effect of angiotensin II (Ang II) on insulin-induced glucose uptake and its intracellular mechanisms in cultured vascular smooth muscle cells (VSMC). Ang II or oxidative stress inhibited insulin-induced glucose uptake, which was reversed by an ERK inhibitor but not by a JNK inhibitor in VSMC. In the chronic mesangioproliferative glomerulonephritis (GN) rat model using uninephrectomy and anti-Thy-1 antibody injection, activation of BMK1 was observed in the glomeruli at day 28 and 56 of GN. In the cultured rat mesangial cells, Ang II and oxidative stress induced BMK1 activation, suggesting that Ang II and oxidative stress involves in an inflammation-induced metabolic syndrome. We also found that BMK1 was activated by H2O2 in a time- and concentration-dependent manner in cultured rat VSMC. The activation of Src tyrosine kinase was also observed which was parallel with the BMK1 activation. We established an experimental model of BMK1 knock downed VSMC using siRNA transfection technology. Furthermore, our results also showed that cell death was increased when H2O2 was added into the BMK1 siRNA transfected VSMC in which BMK1 expression was inhibited. From these findings, it was suggested that BMK1 may play an essential role in protecting cells from oxidative stress-induced apoptosis, which is mediated by Src-mediated signaling pathway. c-Src and BMK1 may be possible targets for the treatment of metabolic syndrome clinically.

Report

(4 results)
  • 2010 Annual Research Report   Final Research Report ( PDF )
  • 2009 Annual Research Report
  • 2008 Annual Research Report
  • Research Products

    (49 results)

All 2011 2010 2009 2008 Other

All Journal Article (24 results) (of which Peer Reviewed: 21 results) Presentation (19 results) Book (2 results) Remarks (4 results)

  • [Journal Article] Big Mitogen-activated Protein Kinase 1 Protects Cultured Rat Aortic Smooth Muscle Cells from Oxidative Damage.2011

    • Author(s)
      Jing Zhao, Yoji Kyotani, Satoyasu Itoh, Hitoshi Nakayama, Minoru Isosaki, Masanori Yoshizumi
    • Journal Title

      J.Pharmacol.Sci. 115 印刷中

    • NAID

      10029894630

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Pharmacology in Health Foods : Preface.2011

    • Author(s)
      Masanori Yoshizumi, Yasuo Matsumura.
    • Journal Title

      J.Pharmacol.Sci. 115(4)

      Pages: 459-460

    • NAID

      10029893214

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Pharmacology in Health Food : Metabolism of Quercetin In Vivo and Its Protective Effect Against Arteriosclerosis.2011

    • Author(s)
      Keisuke Ishizawa, Masanori Yoshizumi, Yoshichika Kawai, Junji Terao, Yoshitaka Kihira, Yasumasa Ikeda, Shuhei Tomita, Koichiro Tsuchiya, Toshiaki Tamaki
    • Journal Title

      J.Pharmacol.Sci. 115(4)

      Pages: 466-470

    • NAID

      10029893264

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Big Mitogen-activated Protein Kinase 1 Protects Cultured Rat Aortic Smooth Muscle Cells from Oxidative Damage2011

    • Author(s)
      Jing Zhao, ほか
    • Journal Title

      J.Pharmacol.Sci.

      Volume: 115(印刷中)

    • NAID

      10029894630

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Pharmacology in Health Foods : Preface2011

    • Author(s)
      Masanori Yoshizumi, ほか
    • Journal Title

      J.Pharmacol.Sci.

      Volume: 115(Advance Publication)

    • NAID

      10029893214

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Pharmacology in Health Food : Metabolism of Quercetin In Vivo and Its Protective Effect Against Arteriosclerosis2011

    • Author(s)
      Keisuke Ishizawa, ほか
    • Journal Title

      J.Pharmacol.Sci.

      Volume: 115(Advance Publication)

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] ERK5 activation enhances mesangial cell viability and collagenmatrix accumulation in rat progressive glomerulonephritis.2010

    • Author(s)
      Urushihara M, Takamatsu M, Shimizu M, Kondo S, Kinoshita Y, Suga K, Kitamura A, Matsuura S, Yoshizumi M, Tamaki T, Kawachi H, Kagami S.
    • Journal Title

      Am.J.Physiol.Renal Physiol. 298

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Role of HIF-1α in T cells as a negative regulator in development of vascular remodeling.2010

    • Author(s)
      Kurobe H, Urata M, Ueno M, Ueki M, OnoS, Izawa-Ishizawa Y, Fukuhara Y, Lei Y, Ripen AM, Kanbara T, Aihara K, Ishizawa K, Akaike M, Gonzalez FJ, Tamaki T, Takahama Y, Yoshizumi M, Kitagawa T, Tomita S.
    • Journal Title

      Arterioscler.Thromb.Vasc.Biol. 30

      Pages: 210-217

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Involvement of mineralocorticoid receptor in high glucose-induced big mitogen-activated protein kinase 1 activation and mesangial cell proliferation.2010

    • Author(s)
      Liu G, Miyata K, Hitomi H, Yao L, Sun GP, Suzaki Y, Hosomi N, Kiyomoto H, Nakano D, Tamaki T, Yoshizumi M, Nishiyama A.
    • Journal Title

      J.Hypertens. 28

      Pages: 536-542

    • Related Report
      2010 Final Research Report
  • [Journal Article] Olmesartan inhibits angiotensin II-induced migration of vascular smooth muscle cells through Src and MAP kinase pathways.2010

    • Author(s)
      Yoji Kyotani, Jing Zhao, Sayuko Tomita, Hitoshi Nakayama, Minoru Isosaki, Masayuki Uno, Masanori Yoshizumi
    • Journal Title

      J.Pharmacol.Sci. 113(2)

      Pages: 161-168

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] 「メタボリックシンドローム対策の実際」チーム医療で取り組むメタボッリクシンドローム対策2010

    • Author(s)
      吉栖正典
    • Journal Title

      循環器plus 10(12)

      Pages: 10-12

    • Related Report
      2010 Final Research Report
  • [Journal Article] Olmesartan inhibits angiotensin II-induced migration of vascular smooth muscle cells through Src and MAP kinase pathways2010

    • Author(s)
      Yoji Kyotani, ほか
    • Journal Title

      J.Pharmacol.Sci.

      Volume: 113,(2) Pages: 161-168

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 「メタボリックシンドローム対策の実際」チーム医療で取り組むメタボッリクシンドローム対策2010

    • Author(s)
      吉栖正典
    • Journal Title

      循環器plus

      Volume: 10,(12) Pages: 10-12

    • Related Report
      2010 Annual Research Report
  • [Journal Article] ERK5 activation enhances mesangial cell viability and collagenmatrix accumulation in rat progressive glomerulonephritis2010

    • Author(s)
      Urushihara M, ほか
    • Journal Title

      Am.J.Physiol.Renal Physiol. 298

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Role of HIF-1α in T cells as a negative regulator in development of vascular remodeling2010

    • Author(s)
      Kurobe H, ほか
    • Journal Title

      Arterioscler.Thromb.Vasc.Biol. 30

      Pages: 210-217

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Involvement of mineralocorticoid receptor in high glucose-induced big mitogen-activated protein kinase 1 activation and mesangial cell proliferation2010

    • Author(s)
      Liu G, ほか
    • Journal Title

      J.Hypertens. 28

      Pages: 536-542

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Neuroprotective effects of pramipexole against tunicamycin-induced celldeath in PC12 cells.2009

    • Author(s)
      Nakayama H, Zhao J, Amany El-Fakharany, Isosaki M, Satoh H, Kyotani Y, Yoshizumi M.
    • Journal Title

      Clin.Exp.Pharmacol.Physiol. 36

      Pages: 1183-1185

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] 最近の話題「サプリメントのEBM」2009

    • Author(s)
      京谷陽司、趙晶、吉栖正典
    • Journal Title

      日本薬理学雑誌 133

      Pages: 297-297

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Neuroprotective effects of pramipexole against tunicamycin-induced cell death in PC12 cells2009

    • Author(s)
      Nakayama H, ほか
    • Journal Title

      Clin.Exp.Pharmacol.Physiol. 36

      Pages: 1183-1185

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 最近の話題「サプリメントのEBM」2009

    • Author(s)
      京谷陽司, ほか
    • Journal Title

      日本薬理学雑誌 133

      Pages: 297-297

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Fluid shear stress inhibits TNF-mediated JNK activation via MEK5-BMK1 in endothelial cells.2008

    • Author(s)
      Li L, Tatake RJ, Natarajan K, Taba Y, Garin G, Tai C, Leung E, Surapisitchat J, Yoshizumi M, Yan C, Abe JI, Berk BC.
    • Journal Title

      Biochem.Biophys.Res.Commun. 370(1)

      Pages: 159-163

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] ER stress is the initial response to polyglutamine toxicity in PC12 cells.2008

    • Author(s)
      Nakayama H, Hamada M, Fujikake N, Nagai Y, Zhao J, Hatano O, Shimoke K, Isosaki M, Yoshizumi M, Ikeuchi T.
    • Journal Title

      Biophys.Res.Commun. 377(2)

      Pages: 550-555

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Fluid shear stress inhibits TNF-mediated JNK activation via MEK5-BMK1 in endothelial cells2008

    • Author(s)
      Li L, ほか
    • Journal Title

      Biochem. Biophys. Res. Commun. 370(1)

      Pages: 159-163

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] ER stress is the initial response to polyglutamine toxicity in PC12 cells2008

    • Author(s)
      Nakayama H, ほか
    • Journal Title

      Biochem. Biophys. Res. Commun. 377(2)

      Pages: 550-555

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Presentation] PC12細胞における細胞表面膜受容体のビオチン化2011

    • Author(s)
      中山均、趙晶、吉栖正典
    • Organizer
      第84回日本薬理学会年会
    • Place of Presentation
      横浜(誌上開催)
    • Year and Date
      2011-03-24
    • Related Report
      2010 Annual Research Report 2010 Final Research Report
  • [Presentation] 酸化ストレスによる血管平滑筋細胞死におけるSrcとBMK1/ERK5の役割2011

    • Author(s)
      趙晶、京谷陽司、富田小優子、中山均、磯崎稔、佐藤広康、吉栖正典
    • Organizer
      第84回日本薬理学会年会
    • Place of Presentation
      横浜(誌上開催)
    • Year and Date
      2011-03-24
    • Related Report
      2010 Annual Research Report 2010 Final Research Report
  • [Presentation] 酸化ストレスによる培養ラット大動脈平滑筋細胞死におけるSrc及びBMK1/ERK5の役割の検討2010

    • Author(s)
      趙晶、京谷陽司、富田小優子、中山均、磯崎稔、佐藤広康、吉栖正典
    • Organizer
      第118回日本薬理学会近畿部会
    • Place of Presentation
      大阪
    • Year and Date
      2010-11-19
    • Related Report
      2010 Annual Research Report 2010 Final Research Report
  • [Presentation] 動脈硬化の発症・進展におけるbig MAP kinase 1の役割2010

    • Author(s)
      吉栖正典
    • Organizer
      第29回財団法人篷庵社研究助成発表会
    • Place of Presentation
      塩野義製薬株式会社中央研究所、大阪
    • Year and Date
      2010-07-23
    • Related Report
      2010 Final Research Report
  • [Presentation] 動脈硬化の発症・進展におけるbig MAP kinase 1の役割2010

    • Author(s)
      吉栖正典
    • Organizer
      第29回財団法人篷庵社研究助成発表会
    • Place of Presentation
      塩野義製薬株式会社中央研究所
    • Year and Date
      2010-07-23
    • Related Report
      2010 Annual Research Report
  • [Presentation] 喫煙が細胞膜受容体に与える影響-外膜蛋白質の特異的定量法の検討2010

    • Author(s)
      中山均、吉栖正典
    • Organizer
      2010年度「住居医学」共同研究成果報告会
    • Place of Presentation
      奈良県立医科大学
    • Year and Date
      2010-03-24
    • Related Report
      2010 Annual Research Report 2010 Final Research Report
  • [Presentation] シンポジウム「健康食品の薬理学」ケルセチンの生体内動態と動脈硬化予防効果2010

    • Author(s)
      石澤啓介、吉栖正典、Dorjsuren Narantungalag、今村優子、池田康将、寺尾純二、土屋浩一郎、玉置俊晃
    • Organizer
      第83回日本薬理学会年会
    • Place of Presentation
      大阪
    • Year and Date
      2010-03-17
    • Related Report
      2010 Final Research Report 2009 Annual Research Report
  • [Presentation] 酸化ストレスによる血管平滑筋細胞死におけるBMK1/ERK5の役割2010

    • Author(s)
      趙晶、京谷陽司、富田小優子、中山均、佐藤広康、磯崎稔、吉栖正典
    • Organizer
      第83回日本薬理学会年会
    • Place of Presentation
      大阪
    • Year and Date
      2010-03-16
    • Related Report
      2010 Final Research Report 2009 Annual Research Report
  • [Presentation] アンジオテンシンIIによるSrcおよびMAPキナーゼを介した血管平滑筋細胞の遊走に対するオルメサルタンの阻害作用2010

    • Author(s)
      京谷陽司、趙晶、富田小優子、佐藤広康、中山均、磯崎稔、宇野雅之、吉栖正典
    • Organizer
      第83回日本薬理学会年会
    • Place of Presentation
      大阪
    • Year and Date
      2010-03-16
    • Related Report
      2010 Final Research Report 2009 Annual Research Report
  • [Presentation] T細胞のHIF-1αは、動脈硬化に伴う血管リモデリングを抑制的に制御する2010

    • Author(s)
      福原弥生、冨田修平, 木平孝高, 池田康将、石澤啓介、土屋浩一郎、吉栖正典、玉置俊晃
    • Organizer
      第39回日本心脈管作動物質学会総会
    • Place of Presentation
      名古屋
    • Year and Date
      2010-02-05
    • Related Report
      2010 Final Research Report
  • [Presentation] T細胞のHIF-1αは、動脈硬化に伴う血管リモデリングを抑制的に制御する2010

    • Author(s)
      福原弥生, ほか
    • Organizer
      第39回 日本心脈管作動物質学会総会
    • Place of Presentation
      名古屋
    • Year and Date
      2010-02-05
    • Related Report
      2009 Annual Research Report
  • [Presentation] PC12細胞における細胞表面膜受容体の同定2010

    • Author(s)
      中山均、吉栖正典
    • Organizer
      第33回日本分子生物学会年回・第83回日本生化学会大会合同年会
    • Place of Presentation
      神戸
    • Related Report
      2010 Annual Research Report 2010 Final Research Report
  • [Presentation] 酸化ストレスによる培養ラット大動脈平滑筋細胞死におけるBMK1/ERK5の役割の検討2009

    • Author(s)
      趙晶、京谷陽司、富田小優子、中山均、磯崎稔、佐藤広康、吉栖正典
    • Organizer
      第116回日本薬理学会近畿部会
    • Place of Presentation
      大津
    • Year and Date
      2009-11-13
    • Related Report
      2010 Final Research Report 2009 Annual Research Report
  • [Presentation] Angiotensin IIによる血管平滑筋細胞の遊走に対するOlmesartanの阻害効果2009

    • Author(s)
      京谷陽司、趙晶、富田小優子、佐藤広康、中山均、磯崎稔、宇野雅之、吉栖正典
    • Organizer
      第115回日本薬理学会近畿部会
    • Place of Presentation
      金沢
    • Year and Date
      2009-06-26
    • Related Report
      2010 Final Research Report
  • [Presentation] Angiotensin IIによる血管平滑筋細胞の遊走に対する Olmesartan の阻害効果2009

    • Author(s)
      京谷陽司, ほか
    • Organizer
      第115回日本薬理学会近畿部会
    • Place of Presentation
      金沢
    • Year and Date
      2009-06-26
    • Related Report
      2009 Annual Research Report
  • [Presentation] PC12細胞におけるポリグルタミン酸誘導小胞体ストレスおよび細胞内シグナリングに対するポリグルタミン鎖長の影響2009

    • Author(s)
      中山均、エルファカラニイ アマニイ、趙晶、磯崎稔、佐藤広康、吉栖正典
    • Organizer
      第82回日本薬理学会年会
    • Place of Presentation
      横浜
    • Year and Date
      2009-03-16
    • Related Report
      2010 Final Research Report 2008 Annual Research Report
  • [Presentation] ウォルトマンニン活性に対するSH還元剤の影響2009

    • Author(s)
      磯崎稔、中山均、佐藤広康、吉栖正典
    • Organizer
      第82回日本薬理学会年会
    • Place of Presentation
      横浜
    • Year and Date
      2009-03-16
    • Related Report
      2010 Final Research Report 2008 Annual Research Report
  • [Presentation] PC12h細胞におけるツニカマイシンによる細胞死に対するプラミペキソールの影響2008

    • Author(s)
      趙晶、中山均、京谷陽司、磯崎稔、佐藤広康、吉栖正典
    • Organizer
      第114回日本薬理学会近畿部会
    • Place of Presentation
      神戸
    • Year and Date
      2008-11-14
    • Related Report
      2010 Final Research Report
  • [Presentation] PC12h細胞におけるツニカマイシンによる細胞死に対するプラミペ牛ソールの影響2008

    • Author(s)
      趙 晶, ほか
    • Organizer
      第114回日本薬理学会近畿部会
    • Place of Presentation
      神戸
    • Year and Date
      2008-11-14
    • Related Report
      2008 Annual Research Report
  • [Book] (第29回)財団法人篷庵社研究助成発表会講演要旨集2010

    • Author(s)
      吉栖正典
    • Total Pages
      61
    • Publisher
      財団法人篷庵社
    • Related Report
      2010 Annual Research Report 2010 Final Research Report
  • [Book] 平成21年度住居医学共同研究成果報告集2010

    • Author(s)
      中山均、吉栖正典
    • Total Pages
      287
    • Publisher
      奈良県立医科大学住居医学大和ハウス寄附講座
    • Related Report
      2010 Annual Research Report 2010 Final Research Report
  • [Remarks] ホームページ等

    • URL

      http://www.naramed-u.ac.jp/~pha/

    • Related Report
      2010 Final Research Report
  • [Remarks]

    • URL

      http://www.naramed-u.ac.jp/~pha/

    • Related Report
      2010 Annual Research Report
  • [Remarks]

    • URL

      http://www.naramed-u.ac.jp/~pha/

    • Related Report
      2009 Annual Research Report
  • [Remarks]

    • URL

      http://www.naramed-u.ac.jp/~pha/

    • Related Report
      2008 Annual Research Report

URL: 

Published: 2008-04-01   Modified: 2016-04-21  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi