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Intracelluar Signaling Mechanism for Stimulation of iNOS Expression in Vascular Smooth Cells by Docosahexaenoic Acid

Research Project

Project/Area Number 14572061
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Biological pharmacy
Research InstitutionHealth Sciences University of Hokkaido

Principal Investigator

HAMAUE Naoya  Health Sciences University of Hokkaido, Faculty of Pharmaceutical Sciences, Instructor, 薬学部, 助教授 (20142987)

Co-Investigator(Kenkyū-buntansha) 浜上 尚也  北海道医療大学, 薬学部, 助手 (70221504)
Project Period (FY) 2002 – 2003
Project Status Completed (Fiscal Year 2003)
Budget Amount *help
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2003: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2002: ¥2,400,000 (Direct Cost: ¥2,400,000)
Keywordsdocosahexaenoic acid / vascular smooth muscle cells / inducible nitric oxide synthase / cyclooxygenase / interleukin-1 / MAP kinase / signal transduction / エイコサペンタエン酸 / 一酸化窒素 / 誘導型NO合成酵素
Research Abstract

The aim of the present project was to clarify the intracellular signaling mechanism for stimulatory effect of docosahexaenoic acid (DI-TA) on inducible nitric oxide synthase (iNOS) expression in cultured vascular smooth muscle cells. When add to the culture medium, DI-IA (1 -30 μM) and, less potently, eicosapentaenoic acid increased the NO production, iNOS protein and mRNA expressions induced by IL-1β. Arachidonic acid had no significant effect. The stimulatory effect of DHA (30 μM) on the NO production was more obvious at lower concentrations of IL-1β. IL-1β increased the phosphorylation of p44/42 MAP kinase, while did not apparently increase the. phosphorylation of p38 MAP kinase. DHA significantly potentiated the IL-1β-induced phosphorylation of p44/42 MAP kinase, while had no significant effect on the phosphorylation of p38 MAP kinase. DHA also potentiated IL-i p-induced cyclooxygenase-2 (COX-2) protein and mRNA expressions in a time-and concentration-dependent manner. However, there was no significant effect on the COX-1 expression. Eicosapentaenoic acid (30 μM) also potentiated IL-1β-induced COX-2 expression, whereas arachidonic acid had no significant effect. DHA potentiated phorbol 12-myristate 13-acetate (PMA)-induced COX-2 protein and mRNA expressions. These results suggest that DMA potentiates iNOS and COX-2 expressions induced by IL-1β through mechanism involving p44/42 MAPK activation. The mild and persistent enhancement by DHA of iNOS and COX-2 expression may contribute to the cardioprotective effects of DI-LA. The present study may contribute to the understanding of basic mechanisms underlying the beneficial effects of DHA on various cardiovascular disorders.

Report

(3 results)
  • 2003 Annual Research Report   Final Research Report Summary
  • 2002 Annual Research Report
  • Research Products

    (13 results)

All Other

All Publications (13 results)

  • [Publications] M.Hirafuji: "Reduced expressions of inducible nitric oxide synthase and cyclo-oxygenase-2 in vascular smooth muscle cells of stroke-prone spontaneously hypertensive rats"Life Sciences. 70. 917-926 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] M.Hirafuji: "Docosahexaenoic acid potentiates interleukin-1β induction of nitric oxide synthase through mechanism involving p44/42 MAPK activation in rat vascular smooth muscle cells"British Journal of Pharmacology. 136. 613-619 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] M.Hirafuji: "Modulation of sphingosine 1-phosphate, a new lipid mediator, on nitric oxide production by vascular smooth muscle cells"Folia Pharmacologica Japonica. 120. 70-72 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] M.Hirafuji: "Cardiovascular protective effects of n-3 polyunsaturated fatty acids with special emphasis on docosahexaenoic acid"Journal of Pharmacological Sciences. 92. 308-316 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Hirafuji, M., Tsunoda, M., Machida, T., Hamaue, N., Endo, T., Miyamoto, A., Minami, M.: "Reduced expressions of inducible nitric oxide synthase and cyclooxygenase-2 in vascular smooth muscle cells of stroke-prone spontaneously hypertensive rats."Life Sci.. 70. 917-926 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Hirafuji, M., Machida, T., Tsunoda, M., Miyamoto, A., Minami, M.: "Docosahexaenoic acid potentiates interleukin-1β induction of nitric oxide synthase through mechanism involving p44/42 MAPK activation in rat vascular smooth muscle cells."Br.J.Pharmacol.. 136. 613-619 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Hirafuji, M., Hamaya, Y., Matsumoto, Y., Machida, T., Minami, M., Kohno, T., Igarashi, Y.: "Modulation of sphingosine 1-phosphate, a new lipid mediator, on nitric oxide production by vascular smooth muscle cells."Folia Pharmacol.Jpn.. 120(Supple 1). 70-72 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Hirafuji, M., Machida, T., Hamaue, N., Minami, M.: "Cardiovascular protective effects of n-3 polyunsaturated fatty acids with special emphasis on docosahexaenoic acid."J.Pharmacol.Sci.. 92. 308-316 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] M.Hirafuji: "Cardiovascular protective effects of n-3 polyunsaturated fatty acids with special emphasis on docosahexaenoic acid"Journal of Pharmacological Sciences. 92(4). 308-316 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] M.Hirafuji: "Enhanced inhibitory effect of 5-hydroxytryptamine on nitric oxide production by vascular smooth muscle cells derived from stroke-prone spontaneously hypertensive rats"Biogenic Amines. (in press). (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] M.Hirafuji: "Reduced expressions of inducible nitric oxide synthase and cyclooxygenase-2 in vascular smooth muscle cells of stroke-prone spontaneously hypertensive rats"Life Science. 70(8). 917-926 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] M.Hirafuji: "Docosahexaenoic acid potentiates interleukin-1β induction of nitric oxide synthase through mechanism involving p44/42 MAPK activation in rat vasucular smooth muscle cells"British Journal of Pharmacology. 136(4). 613-619 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 平藤 雅彦: "血管平滑筋細胞でのNO産生系に及ぼす新規脂質メディエーター、スフィンゴシン1-リン酸の影響"日本薬理学雑誌. 120(補冊1). 70-72 (2002)

    • Related Report
      2002 Annual Research Report

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Published: 2002-04-01   Modified: 2016-04-21  

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