Construction of a Bank of the Cells Lacking Phosphoinositide-Metabolizing Enzymes

• Project/Area Number: 20590060
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Biological pharmacy
• Research Institution: Hiroshima University
• Principal Investigator: HAZEKI Osamu Hiroshima University, 大学院・医歯薬学総合研究科, 教授 (80142751)
• Project Period (FY): 2008 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2010: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2009: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2008: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
• Keywords: イノシトールリン脂質代謝 / shRNA / RAW264.7細胞 / ファゴサイトーシス / ファゴソーム / PtdIns(3)P / eGFP-FYVE / PTEN / VPS34 / RAW264.7 / phagocytosis / PIKFYVE / PI3K-CIIα / Class I PI3K / SHIP-1 / p110α / p110β

Research Abstract

A series of cells lacking phosphoinositide-metabolizing enzymes was prepared from RAW264.7 macrophages. The analysis with the cells identified a group of enzymes functioning in phagocytotic events. Selective inhibitors of phosphoinositidemetabolizing enzymes are attractive candidates for medicines such as anti-cancer drugs. The bank of the cells can be used to determine the specificity of the inhibitors.

Research Products

• [Journal Article] C5a controls TLR-induced IL-10 and IL-12 production independent of phosphatidyllinositol 3-kinase (2011)
  • Author(s): Okazaki N, Hazeki K, Izumi T, Nigorikawa K, Hazeki O
  • Journal Title: J Biochem 149 Pages: 265-274
  • Peer Reviewed
• [Journal Article] C5a controls TLR-induced IL-10 and IL-12 production independent of phosphatidyl-inositol 3-kinase (2011)
  • Author(s): Okazaki N, et al.
  • Journal Title: J Biochem Volume: 149 Pages: 265-274
  • Peer Reviewed
• [Journal Article] Acute effect of melatonin and its time of administration on core body temperature and heart rate in cynomolgus monkeys (2010)
  • Author(s): Inui Y, Hazeki O
  • Journal Title: J Toxicol Sci 35 Pages: 383-391
  • NAID: 10026469845
  • Peer Reviewed
• [Journal Article] Acute effect of melatonin and its time of administration on core body temperature and heart rate in cynomolgus monkeys (2010)
  • Author(s): Inui Y, Hazeki O
  • Journal Title: J Toxicol Sci Volume: 35 Pages: 383-391
  • NAID: 10026469845
  • Peer Reviewed
• [Journal Article] Specific role of phosphoinositide 3-kinase p110{alpha} in the regulation of phagocytosis and pinocytosis in macrophages (2009)
  • Author(s): Tamura N, Hazeki K, Okazaki N, Kametani Y, Murakami H, Takaba Y, Ishikawa Y, Nigorikawa K, Hazeki O
  • Journal Title: Biochem J 423 Pages: 99-108
  • Peer Reviewed
• [Journal Article] Analysis of binding site for the novel small-molecule TLR4 signal transduction inhibitor TAK-242 and its therapeutic effects in mouse sepsis model (2009)
  • Author(s): Takashima K, Matsunaga N, Yoshimatsu M, Hazeki K, Kaisho T, Uekata M, Hazeki O, Akira S, Iizawa Y, Ii M
  • Journal Title: Br J Pharmacol 157 Pages: 1250-1262
  • Peer Reviewed
• [Journal Article] Specific role of phosphoinositide 3-kinase p110{alpha} in the regulation of phago cytosis and pinocytosis in macrophages (2009)
  • Author(s): Tamura N, et al.
  • Journal Title: Biochem J 423 Pages: 99-108
  • Peer Reviewed
• [Journal Article] Analysis of binding site for the novel small-molecule TLR4 signal transduction inhibitor TAK-242 and its therapeutic effects in mouse sepsis model (2009)
  • Author(s): Takashima K, et al.
  • Journal Title: Br J Pharmacol 157 Pages: 1250-1262
  • Peer Reviewed
• [Journal Article] Enhancement of antitumor natural killer cell activation by orally administered Spprulina extract in mice (2009)
  • Author(s): Akao Y, et al.
  • Journal Title: Cancer Sci 100 Pages: 1494-1501
  • Peer Reviewed
• [Journal Article] Negative regulation of class IA phosphoinositide 3-kinase by protein kinase C{delto}l limits Fc{gamma} receptor-mediated phagocytosis in macrophages (2009)
  • Author(s): Hazeki K, et al.
  • Journal Title: J Biochem 145 Pages: 87-94
  • Peer Reviewed
• [Journal Article] Critical roles of the p110β subtype of phosphoinositide 3-kinase in lipopolysaccharide-induced Akt activation and negativeregulation of nitrite production in RAW 264,7 cells (2008)
  • Author(s): Tsukamoto, K, et al.
  • Journal Title: J, immunol. 180 Pages: 2054-2061
  • Peer Reviewed
• [Journal Article] IRAK4-dependent degradation of IRAK1 is a negative feedback signal for TLR-mediated NF_kB activation (2008)
  • Author(s): Kubo-Murai M., et al.
  • Journal Title: J. Biochem. 143 Pages: 295-302
  • Peer Reviewed
• [Presentation] 好中球の活性酸素産生を制御するPI3-キナーゼサブタイプの解明 (2010)
  • Author(s): 熊澤崇, 濁川清美, 櫨木薫, 櫨木修
  • Organizer: 第51回日本生化学会中国・四国支部例会
  • Place of Presentation: 山口
  • Year and Date: 2010-05-15
• [Presentation] マクロファージの貪食におけるイノシトールリン脂質の動態の解明 (2010)
  • Author(s): 高場雄貴、櫨木薫、櫨木修
  • Organizer: 第51回日本生化学会中国・四国支部例会
  • Place of Presentation: 山口
  • Year and Date: 2010-05-15
• [Presentation] 好中球の活性酸素産生を制御するPI3-キナーゼサブタイプの解明 (2010)
  • Author(s): 熊澤崇, ほか
  • Organizer: 第51回日本生化学会中国・四国支部例会
  • Place of Presentation: 山口大学
  • Year and Date: 2010-05-15
• [Presentation] マクロファージの貪食におけるイノシトールリン脂質の動態の解明 (2010)
  • Author(s): 高場雄貴, ほか
  • Organizer: 第51回日本生化学会中国・四国支部例会
  • Place of Presentation: 山口大学
  • Year and Date: 2010-05-15
• [Presentation] 好中球の活性酸素産生を制御するイノシトールリン脂質3キナーゼ(PI3K)アイソフォームの解明 (2009)
  • Author(s): 伊藤裕太、濁川清美、櫨木薫、櫨木修
  • Organizer: 第82回日本生化学会大会
  • Place of Presentation: 神戸
  • Year and Date: 2009-10-24
• [Presentation] Toll様受容体を介するIL-12産生におけるイノシトールリン脂質3キナーゼ(PI3K)のサブタイプ特異的な役割の解明 (2009)
  • Author(s): 泉達宏, 小縣旬, 亀谷由紀子, 濁川清美, 櫨木薫, 櫨木修
  • Organizer: 第82回日本生化学会大会
  • Place of Presentation: 神戸
  • Year and Date: 2009-10-24
• [Presentation] 抗体依存性食作用に関与するイノシトールリン脂質3キナーゼのサブタイプの解明 (2009)
  • Author(s): 小縣旬, 濁川清美, 櫨木薫, 櫨木修
  • Organizer: 第82回日本生化学会大会
  • Place of Presentation: 神戸
  • Year and Date: 2009-10-24
• [Presentation] イノシトールリン脂質3キナーゼ(PI3K)γのCpG-DNA刺激に特異的な役割-IL-10産生の増強とIL-12産生の抑制 (2009)
  • Author(s): 亀谷由紀子, 泉達宏, 小縣旬, 濁川清美, 櫨木薫, 櫨木修
  • Organizer: 第82回日本生化学会大会
  • Place of Presentation: 神戸
  • Year and Date: 2009-10-24
• [Presentation] マスト細胞のアレルギー反応におけるイノシトールリン脂質3キナーゼ(PI3K)の関与 (2009)
  • Author(s): 原里奈, 濁川清美, 櫨木薫, 櫨木修
  • Organizer: 第82回日本生化学会大会
  • Place of Presentation: 神戸
  • Year and Date: 2009-10-24
• [Presentation] 好中球の活性酸素産生に関わるPI3-キナーゼのサブタイプの解明 (2009)
  • Author(s): 伊藤裕太、濁川清美、櫨木薫、櫨木修
  • Organizer: 第8回生命科学研究会
  • Place of Presentation: 神戸
  • Year and Date: 2009-06-26
• [Presentation] Differential regulation of phagocytosis, macropinocytosis and micropinocytosis by phosphoinositide 3-kinase p110{alpha} in macrophages (2008)
  • Author(s): 田村奈美子、櫨木薫、櫨木修
  • Organizer: 第38回日本免疫学会総会
  • Place of Presentation: 京都
  • Year and Date: 2008-12-03
• [Presentation] Differential regulation of phagocytosis, macropinocytosis, and micropinocytosis by phosphoinositide 3-kinase p110α in macro-phages (2008)
  • Author(s): 田村奈美子ら
  • Organizer: 第38回日本免疫学会総会
  • Place of Presentation: 国立京都国際会館
  • Year and Date: 2008-12-03
• [Presentation] C5a inhibits LPS-induced IL-12 production by activation of phosphoinositide 3-kinase other than p110{gamma} (2008)
  • Author(s): 岡崎夏実、櫨木薫、櫨木修
  • Organizer: 第38回日本免疫学会総会
  • Place of Presentation: 京都
  • Year and Date: 2008-12-02
• [Presentation] (招待講演)ナフトキノン化合物のインスリンシグナル経路活性化作用 (2008)
  • Author(s): 櫨木修
  • Organizer: 生体キノン研究会
  • Place of Presentation: 大阪
  • Year and Date: 2008-09-26
• [Presentation] (招待講演)Class IA型PI3-kinaseのサブタイプ特異的な機能 (2008)
  • Author(s): 櫨木修
  • Organizer: 千葉大学大学院薬学研究院特別講演
  • Place of Presentation: 千葉
  • Year and Date: 2008-07-24
• [Presentation] マクロファージのエンドサイトーシスの制御における PI3K各サブタイプの役割 (2008)
  • Author(s): 田村奈美子、櫨木薫、濁川清美、櫨木修
  • Organizer: 第7回生命科学研究会
  • Place of Presentation: 別府
  • Year and Date: 2008-05-29