Exploring the roles of sphingosine 1-phosphate(S1P), a lipid mediator, in ischemic heart

• Project/Area Number: 21590933
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Circulatory organs internal medicine
• Research Institution: Kagawa University
• Principal Investigator: IGARASHI Junsuke 香川大学, 医学部, 准教授 (20346638)
• Co-Investigator(Kenkyū-buntansha): KOSAKA Hiroaki 香川大学, 医学部, 教授 (60158897) ; HASHIMOTO Takeshi 香川大学, 医学部, 助教 (80380153)
• Project Period (FY): 2009 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2011: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2010: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2009: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
• Keywords: 心筋虚血 / 脂質メディエーター / スフィンゴ脂質 / 細胞内情報伝達機構 / 受容体シグナリング / caveolin-1 / サイトカイン

Research Abstract

We performed experimental research to explore the roles of S1P and related molecules in ischemic heart diseases. It has been established that sphingolipid-enriched micro-compartments of peripheral plasma membrane termed caveolae and their structural component protein caveolin-1 play key roles in mediating S1P signaling. We determined that a cytokine TGFβ1 promotes S1P signaling in cultured vascular endothelial cells by attenuating caveolin-1 expression. We also discovered that steroid hormones are capable of up-regulating caveolin-1 to down-regulated VEGF receptor signaling pathways.

Research Products

• [Journal Article] Lipid peroxidation-induced VEGF expression in the skin of KKAy obese mice (2011)
  • Author(s): Nakai K, Yoneda, K, Ishihara Y, Ohmori K, Moriue T, Igarashi J, Kohno M, Kosaka H and Kubota Y
  • Journal Title: Experimental Dermatology Volume: 20(5) Pages: 388-93
  • Peer Reviewed
• [Journal Article] Reaction mechanism of single subunit NADH-ubiquinone oxidoreductase(Ndi1) from Saccharomyces cerevisiae : evidence for a ternary complex mechanism (2011)
  • Author(s): Yang Y, Yamashita T, Nakamaru-Ogiso E, Hashimoto T, Murai M, Igarashi J, Miyoshi H, Mori N, Matsuno-Yagi A, Yagi T and Kosaka H
  • Journal Title: J Biol Chem Volume: 286(11) Pages: 9287-97
  • Peer Reviewed
• [Journal Article] Reaction mechanism of single subuuit NADH-ubiquinone oxidoreductase (Ndi1) from Saccharomyces cerevisiae : evidence for a ternary complex mechanism (2011)
  • Author(s): Yang Y., et al
  • Journal Title: J Biol Chem Volume: 286 Issue: 11 Pages: 9287-97
  • DOI: 10.1074/jbc.m110.175547
  • Peer Reviewed
• [Journal Article] Lipid peroxidation-induced VEGF expression in the skin of KKAy obese mice (2011)
  • Author(s): Nakai K., et al
  • Journal Title: Experimental Dermatology Volume: 20 Issue: 5 Pages: 388-93
  • DOI: 10.1111/j.1600-0625.2010.01223.x
  • Peer Reviewed
• [Journal Article] A novel nucleic acid analogue shows strong angiogenic activity. (2011)
  • Author(s): 塚本郁子
  • Journal Title: Biochem Biophys Res Commun. Volume: 399 Pages: 699-704
  • Peer Reviewed
• [Journal Article] Reaction mechanism of single subunit NADH-ubiquinone oxidoreductase (Ndi1) from Saccharomyces cerevisiae : evidence for a ternary complex mechanism. (2011)
  • Author(s): 楊宇
  • Journal Title: J.Biol.Chem Volume: 286 Pages: 699-704
  • Peer Reviewed
• [Journal Article] Expression of wild-type, but not mutant, loricrin causes programmed cell death in HaCaT keratinocytes (2010)
  • Author(s): Yoneda K, Demitsu T, Manabe M, Igarashi J, Kosaka H, Inagaki N, Takahashi H, Kon A, Kakuai M and Kubota Y
  • Journal Title: The Journal of Dermatology Volume: 37(11) Pages: 956-64
  • NAID: 10027572660
  • Peer Reviewed
• [Journal Article] A novel nucleic acid analogue shows strong angiogenic activity (2010)
  • Author(s): Tsukamoto I, Sakakibara N, Maruyama T, Igarashi J, Kosaka H, Kubota Y, Tokuda M, Ashino H, Hattori K, Tanaka S, Kawata M and Konishi R
  • Journal Title: Biochem Biophys Res Commun Volume: 399(4) Pages: 699-704
  • Peer Reviewed
• [Journal Article] Activation of vascular endothelial growth factor receptor 2 in a cellular model of loricrin keratoderma (2010)
  • Author(s): Yoneda K, Demitsu T, Nakai K, Moriue T, Ogawa W, Igarashi J, Kosaka H, and Kubota Y
  • Journal Title: J Biol Chem Volume: 285(21) Pages: 16184-94
  • Peer Reviewed
• [Journal Article] Activation of vascular endothelial growth factor receptor 2 in a cellular model of loricrin keratoderma. (2010)
  • Author(s): 米田耕造
  • Journal Title: J.Biol.Chem Volume: 285 Pages: 16184-16194
  • Peer Reviewed
• [Journal Article] Expression of wild-type, but not mutant, loricrin causes programmed cell death in HaCaT keratinocytes. (2010)
  • Author(s): 米田耕造
  • Journal Title: The Journal of Dermatology. Volume: 37 Pages: 956-964
  • Peer Reviewed
• [Journal Article] Transforming Growth Factor-{ beta} 1 Down-Regulates Caveolin-1 Expression And Enhances Sphingosine 1-Phosphate Signaling In Cultured Vascular Endothelial Cells (2009)
  • Author(s): Igarashi J, Shoji K, Hashimoto T, Moriue T, Yoneda K, Takamura T, Yamashita T, Kubota Y, and Kosaka H
  • Journal Title: Am. J. Physiol.(Cell Physiology) Volume: 297
  • Peer Reviewed
• [Journal Article] Transforming Growth Factor-{beta}1 Down-Regulates Caveolin-1 Expression And Enhances Sphingosine 1-Phosphate Signaling In Cultured Vascular Endothelial Cells (2009)
  • Author(s): 五十嵐淳介
  • Journal Title: Am.J.Physiol. (Cell Physiology) 297
  • Peer Reviewed
• [Journal Article] Sphingosine kinase is induced in mouse 3T3-L1 cells and promotes adipogenesis (2009)
  • Author(s): 橋本剛
  • Journal Title: Journal of Lipid Research 50 Pages: 602-610
  • Peer Reviewed
• [Journal Article] HB-EGF-induced VEGF production and eNOS activation depend on both PI3 kinase and MAP kinase in HaCaT cells (2009)
  • Author(s): 中井浩三
  • Journal Title: J Dermatol Sci. 55 Pages: 170-178
  • Peer Reviewed
• [Presentation] TGFβ1 down-regulates VEGFR-2 and attenuates VEGF-induced activation of protein kinase Akt in cultured endothelial cells (2012)
  • Author(s): Igarashi J., et al
  • Organizer: 日本生理学会
  • Place of Presentation: 長野県松本文化会館
  • Year and Date: 2012-03-29
• [Presentation] TGFβ1 down-regulates VEGFR-2 and attenuates VEGF-induced activation of protein kinase Akt in cultured endothelial cells (2012)
  • Author(s): Igarashi J, Shoji K, Hashimoto T, Tsukamoto I, Yoneda K, Kubota Y, and Kosaka H
  • Organizer: 日本生理学会
  • Place of Presentation: 長野県松本市
  • Year and Date: 2012-03-28
• [Presentation] Glucocorticoid(GC) up-regulates expression of caveolin-1(cav-1) and attenuates VEGF responses in endothelial cells(EC) (2011)
  • Author(s): Igarashi J, Shoji K, Hashimoto T, Yoneda K, Moriue T, Tsukamoto I, Kubota Y, and Kosaka H
  • Organizer: 日本生理学会
  • Place of Presentation: 誌上開催
  • Year and Date: 2011-03-29
• [Presentation] 糖質コルチコイド(GC : glucocorticoid)はcaveolin-1(cav-1)の誘導を介して血管内皮細胞(EC : endothelial cells)におけるVEGF反応を減弱させる (2011)
  • Author(s): 五十嵐淳介
  • Organizer: 第88回日本生理学会
  • Place of Presentation: 誌上開催
  • Year and Date: 2011-03-29
• [Presentation] ステロイド受容体アゴニストはcaveolin-1(cav-1)発現を増加させることで血管内皮のVEGF反応を抑制する (2011)
  • Author(s): 五十嵐淳介、小路和代、橋本剛、米田耕造、森上徹也、塚本郁子、窪田泰夫、小坂博昭
  • Organizer: 日本心脈管作動物質学会
  • Place of Presentation: 香川県高松市
  • Year and Date: 2011-02-04
• [Presentation] ステロイド受容体アゴニストはcaveolin-1(cav-1)発現を増加させることで血管内皮のVEGF反応を抑制する (2011)
  • Author(s): 五十嵐淳介
  • Organizer: 第40回日本心脈管作動物質学会
  • Place of Presentation: 香川県高松市サンポート高松
  • Year and Date: 2011-02-04
• [Presentation] Steroid Hormones Induce Caveolin-1(cav-1) And Attenuate vascular endothelial growth factor(VEGF) Responses In Cultured Vascular Endothelial Cells(EC) (2010)
  • Author(s): Igarashi J, Hashimoto T, Shoji K, Yoneda K, Kubota Y, and Kosaka H
  • Organizer: American Heart Association Scientific Sessions
  • Place of Presentation: アメリカ合衆国イリノイ州シカゴ市
  • Year and Date: 2010-11-16
• [Presentation] Steroid Hormones Induce Caveolin-1(cav-1) And Attenuate Vascular Endothelial Growth Factor (VEGF) Responses In Cultured Vascular Endothelial Cells(EC) (2010)
  • Author(s): 五十嵐淳介
  • Organizer: American Heart Association Scientific Sessions
  • Place of Presentation: アメリカ合衆国イリノイ州シカゴ市McCormick Place
  • Year and Date: 2010-11-16