2003 Fiscal Year Final Research Report Summary
Intracelluar Signaling Mechanism for Stimulation of iNOS Expression in Vascular Smooth Cells by Docosahexaenoic Acid
| Project/Area Number |
14572061
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Biological pharmacy
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| Research Institution | Health Sciences University of Hokkaido |
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Principal Investigator |
HAMAUE Naoya Health Sciences University of Hokkaido, Faculty of Pharmaceutical Sciences, Instructor, 薬学部, 助教授 (20142987)
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| Co-Investigator(Kenkyū-buntansha) |
浜上 尚也 北海道医療大学, 薬学部, 助手 (70221504)
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| Project Period (FY) |
2002 – 2003
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| Keywords | docosahexaenoic acid / vascular smooth muscle cells / inducible nitric oxide synthase / cyclooxygenase / interleukin-1 / MAP kinase / signal transduction |
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| 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.
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[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)
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[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)
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