Exploration of the drug for atherosclerosis which related to the proliferation of smooth muscle cells-induced rupture of vascular redox homeostasis

• Project/Area Number: 23790190
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Medical pharmacy
• Research Institution: Gifu Pharmaceutical University
• Principal Investigator: KAMIYA Tetsuro 岐阜薬科大学, 薬学部, 助教 (60453057)
• Project Period (FY): 2011 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2012: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2011: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
• Keywords: EC-SOD / MEK/ERK / フラボノイド / FCS / Flavonoid

Research Abstract

We investigated the regulation of EC-SOD during FCS-induced VSMCs proliferation to explore the drug for atherosclerosis. We confirmed that the reduction of EC-SOD during FCS-induced cells proliferation through MEK/ERK-derived signaling. Further, pretreatment with flavonoids such as luteolin and chrysoeriol significantly suppressed FCS-triggered EC-SOD reduction. Overall, we suggested that the regulation of EC-SOD might lead to improve vascular diseases.

Research Products

• [Journal Article] Epigenetic regulation of extracellular-superoxide dismutase in human monocytes. (2013)
  • Author(s): Tetsuro Kamiya, Masatomo Machiura, Junya Makino, Hirokazu Hara, Isao Hozumi and Tetsuo Adachi
  • Journal Title: Free Radic. Biol. Med. Volume: 61 Pages: 197-205
  • Peer Reviewed
• [Journal Article] Effect of endoplasmic reticulum (ER) stress inducer thapsigargin on the expression of extracellular-superoxide dismutase in mouse 3T3-L1 adipocytes (2013)
  • Author(s): Tetsuro Kamiya, Hirokazu Hara, Tetsuo Adachi
  • Journal Title: Journal of Clinical Biochemistry and Nutrition Volume: 52 Issue: 2 Pages: 101-105
  • DOI: 10.3164/jcbn.12-46
  • NAID: 130004466711
  • ISSN: 0912-0009, 1880-5086
  • Peer Reviewed
• [Journal Article] Epigenetic regulation of extracellular-superoxide dismutase in human monocytes. (2013)
  • Author(s): Tetsuro Kamiya, Masatomo Machiura, Junya Makino, Hirokazu Hara, Isao Hozumi, Tetsuo Adachi
  • Journal Title: Free Radical Biology and Medicine Volume: in press Pages: 197-205
  • DOI: 10.1016/j.freeradbiomed.2013.04.013
  • Peer Reviewed
• [Journal Article] Effect of endoplasmic reticulum (ER) stress inducer thapsigargin on the expression of extracellular-superoxide dismutase in mouse 3T3-L1 adipocytes. (2012)
  • Author(s): Tetsuro Kamiya, Hirokazu Hara and Tetsuo Adachi
  • Journal Title: J. Clin.Biochem. Nutr. Volume: 52 Pages: 101-105
  • NAID: 130004466711
  • Peer Reviewed
• [Journal Article] Ethanol extract of Brazilian red propolis induces apoptosis in human breast cancer MCF-7 cells through endoplasmic reticulum stress (2012)
  • Author(s): Tetsuro Kamiya, Hiroko Nishihara, Hirokazu Hara and Tetsuo Adachi
  • Journal Title: J. Agric.Food Chem. Volume: 60 Pages: 11065-11070
  • Peer Reviewed
• [Journal Article] TPA induces the expression of EC-SOD in human monocytic THP-1 cells: involvement of PKC, MEK/ERK and NOX-derived ROS. (2012)
  • Author(s): Junya Makino, Tetsuro Kamiya, Hirokazu Hara and Tetsuo Adachi
  • Journal Title: Free Radic. Res. Volume: 46 Pages: 637-644
  • Peer Reviewed
• [Journal Article] Propolis suppresses CdCl2-induced cytotoxicity of COS7 cells through the prevention of intracellular ROS accumulation. (2012)
  • Author(s): Tetsuro Kamiya, Misato Izumi, Hirokazu Hara and Tetsuo Adachi
  • Journal Title: Biol.Pharm. Bull. Volume: 35 Pages: 1126-1131
  • Peer Reviewed
• [Journal Article] Ethanol extract of Brazilian red propolis induces apoptosis in human breast cancer MCF-7 cells through endoplasmic reticulum stress. (2012)
  • Author(s): Tetsuro Kamiya, Hiroko Nishihara, Hirokazu Hara, Tetsuo Adachi
  • Journal Title: Journal of Agricultural Food Chemistry Volume: 60 Issue: 44 Pages: 11065-11070
  • DOI: 10.1021/jf303004n
  • Peer Reviewed
• [Journal Article] TPA induces the expression of EC-SOD in human monocytic THP-1 cells: Involvement of PKC, MEK/ERK and NOX-derived ROS. (2012)
  • Author(s): Junya Makino, Tetsuro Kamiya, Hirokazu Hara, Tetsuo Adachi
  • Journal Title: Free Radical Research Volume: 46 Pages: 637-644
  • Peer Reviewed
• [Journal Article] Propolis suppresses CdCl2-induced cytotoxicity of COS7 cells through the prevention of intracellular ROS accumulation. (2012)
  • Author(s): Tetsuro Kamiya, Misato Izumi, Hirokazu Hara, Tetsuo Adachi
  • Journal Title: Biological and Pharmaceutical Bulletin Volume: in press
  • Peer Reviewed
• [Journal Article] Extracellular-superoxide dismutase expression in COS7 cells exposed to cadmium chloride. (2011)
  • Author(s): Aya Obara, Tetsuro Kamiya, Misato Izumi, Hirokazu Hara, Harutaka Yamada and Tetsuo Adachi
  • Volume: 34
  • Pages: 1443-1447
  • NAID: 130001872438
  • Peer Reviewed
• [Journal Article] Extracellular-superoxide dismutase expression in COS7 cells exposed to cadmium chloride. (2011)
  • Author(s): Aya Obara, Tetsuro Kamiya, Misato Izumi, Hirokazu Hara, Harutaka Yamada, Tetsuo Adachi
  • Journal Title: Biological and Pharmaceutical Bulletin Volume: 34 Pages: 1443-1447
  • NAID: 130001872438
  • Peer Reviewed
• [Journal Article] Luteolin suppresses the differentiation of THP-1 cells through the inhibition of NOX2 mRNA and the membrane translocation of p47phox.
  • Author(s): Junya Makino, Ryohei Nakanishi, Tetsuro Kamiya, (他4名)
  • Journal Title: J. Nat. Prod. Volume: (in press)
  • Peer Reviewed
• [Presentation] FCS誘導性血管平滑筋細胞増殖過程におけるEC-SOD発現変動 (2013)
  • Author(s): 神谷 哲朗、橋本 茉緒、原 宏和、二ノ宮 真之、纐纈 守、足立 哲夫
  • Organizer: 日本薬学会第133年会
  • Place of Presentation: 神奈川
  • Year and Date: 2013-03-29
• [Presentation] FCS誘導性血管平滑筋細胞増殖過程におけるEC-SOD発現変動 (2013)
  • Author(s): 神谷 哲朗、橋本 茉緒、原 宏和、二ノ宮 真之、纐纈 守、足立 哲夫
  • Organizer: 日本薬学会第133年会
  • Place of Presentation: パシフィコ横浜
• [Presentation] 低酸素状態下のCOS7細胞におけるEC-SOD発現調節機構としてのエピジェネティクス (2012)
  • Author(s): 神谷 哲朗、服部 脩平、原 宏和、山田 晴生、足立 哲夫
  • Organizer: 第24回腎とフリーラジカル研究会
  • Place of Presentation: 東京
  • Year and Date: 2012-10-06
• [Presentation] ヒト単球系細胞株におけるEC-SOD発現のエピジェネティック制御機構 (2012)
  • Author(s): 神谷 哲朗、牧野 純也、町浦 雅量、原宏和、足立 哲夫
  • Place of Presentation: 徳島
  • Year and Date: 2012-06-07
• [Presentation] プロポリスのカドミウム誘導性腎尿細管上皮細胞傷害抑制作用 (2012)
  • Author(s): 神谷 哲朗、和泉 美里、原 宏和、足立 哲夫
  • Place of Presentation: 北海道
  • Year and Date: 2012-03-29
• [Presentation] ヒト単球系細胞株におけるEC-SOD発現のエピジェネティック制御機構 (2012)
  • Author(s): 神谷 哲朗、牧野 純也、町浦 雅量、原 宏和、足立 哲夫
  • Organizer: 第65回日本酸化ストレス学会
  • Place of Presentation: あわぎんホール
• [Presentation] 低酸素状態下のCOS7細胞におけるEC-SOD発現調節機構としてのエピジェネティクス (2012)
  • Author(s): 神谷 哲朗、服部 脩平、原 宏和、山田 晴生、足立 哲夫
  • Organizer: 第24回腎とフリーラジカル研究会
  • Place of Presentation: 興和創薬ホール
• [Presentation] プロポリスのカドミウム誘導性腎尿細管上皮細胞傷害抑制作用 (2012)
  • Author(s): 神谷 哲朗、和泉 美里、原 宏和、足立 哲夫
  • Organizer: 日本薬学会第132年会
  • Place of Presentation: 北海道大学高等教育推進機構（北海道）
• [Presentation] TPAによるTHP-1細胞分化過程におけるEC-SOD発現変動 (2011)
  • Author(s): 神谷 哲朗、牧野 純也、町浦 雅量、原 宏和、足立 哲夫
  • Place of Presentation: 北海道
  • Year and Date: 2011-07-02
• [Presentation] TPAによるTHP-1細胞分化過程におけるEC-SOD発現変動 (2011)
  • Author(s): 神谷 哲朗、牧野 純也、町浦 雅量、原 宏和、足立 哲夫
  • Organizer: 第64回日本酸化ストレス学会学術集会
  • Place of Presentation: ルスツリゾートホテル＆コンベンション（北海道）
• [Book] 腎とフリーラジカル第11集 (2013)
  • Author(s): 神谷 哲朗、小原 彩、和泉 美里、原 宏和、山田 晴生、足立 哲夫
  • Publisher: 東京医学社
• [Book] 腎とフリーラジカル第11集 (2013)
  • Author(s): 神谷 哲朗、小原 彩、和泉 美里、原 宏和、山田 晴生、足立 哲夫
  • Total Pages: 178
  • Publisher: 東京医学社
• [Book] Regulation of EC-SOD in hypoxic adipocytes. (2012)
  • Author(s): Tetsuro Kamiya, Hirokazu Hara, Naoki Inagaki and Tetsuo Adachi
  • Publisher: In Tech, Medic. Chem. Drug Design
• [Book] MEDICINAL CHEMISTRY AND DRUG DESIGN (2012)
  • Author(s): Tetsuro Kamiya, Hirokazu Hara, Naoki Inagaki, Tetsuo Adachi
  • Total Pages: 406
  • Publisher: INTECH
• [Remarks] ホームページ
  • URL: http://www.gifu-pu.ac.jp/lab/rinyaku/index.html
• [Remarks] 第65回日本酸化ストレス学会学術奨励賞受賞、2012、06、07、徳島
• [Remarks] 岐阜薬科大学 医療薬剤学大講座 臨床薬剤学研究室ホームページ
  • URL: http://www.gifu-pu.ac.jp/lab/rinyaku/index.html