Eicosapentaenoic acid (EPA) induces Ca2+‐independent activation and translocation of endothelial nitric oxide synthase and endothelium‐dependent vasorelaxation

FEBS Letters

Omura, Masato²  Mogami, Kimiko¹  Kobayashi, Sei¹  Mizukami, Yoichi¹  Todoroki-Ikeda, Natsuko¹  Matsuzaki, Masunori²  Miyake, Teruki¹ 

[1] First Department of Physiology, School of Medicine, Yamaguchi University, 1-1-1 Minami-Kogushi, Ube 755-8505, Japan;Second Department of Internal Medicine, School of Medicine, Yamaguchi University, 1-1-1 Minami-Kogushi, Ube 755-8505, Japan

关键词: Eicosapentaenoic acid;    Nitric oxide;    Endothelial cell;    Vasorelaxation;    Smooth muscle;    Cytosolic Ca2+;    EPA;    eicosapentaenoic acid;    NO;    nitric oxide;    [Ca2+]i;    intracellular Ca2+ concentration;    L-NAME;    Nω -nitro-L-arginine methyl ester;    eNOS;    endothelial nitric oxide synthase;    PUFA;    polyunsaturated fatty acids;    BAPTA;    1;    2-bis-o-aminophenoxythamine-N′;    N′;    N′-tetraacetic acid;    NOS;    nitric oxide synthase;    CaM;    calmodulin;    HUVEC;    human cultured umbilical vein endothelial cells;    DPA;    docosapentaenoic acid;    DHA;    docosahexaenoic acid;    DAN;    2;    3-diaminonaphthalene;    TRIM;    1-(2-trifluoromethylphenyl) imidazole;    BK;    bradykinin;    iNOS;    inducible NOS;    PSS;    physiological salt solution;    ION;    ionomycin;   

DOI  :  10.1016/S0014-5793(00)02351-6

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Eicosapentaenoic acid (EPA), but not its metabolites (docosapentaenoic acid and docosahexaenoic acid), stimulated nitric oxide (NO) production in endothelial cells in situ and induced endothelium-dependent relaxation of bovine coronary arteries precontracted with U46619. EPA induced a greater production of NO, but a much smaller and more transient elevation of intracellular Ca²⁺ concentration ([Ca²⁺]i), than did a Ca²⁺ ionophore (ionomycin). EPA stimulated NO production even in endothelial cells in situ loaded with a cytosolic Ca²⁺ chelator 1,2-bis-o-aminophenoxythamine-N′,N′,N′-tetraacetic acid, which abolished the [Ca²⁺]i elevations induced by ATP and EPA. The EPA-induced vasorelaxation was inhibited by N ^ω -nitro-L-arginine methyl ester. Immunostaining analysis of endothelial NO synthase (eNOS) and caveolin-1 in cultured endothelial cells revealed eNOS to be colocalized with caveolin in the cell membrane at a resting state, while EPA stimulated the translocation of eNOS to the cytosol and its dissociation from caveolin, to an extent comparable to that of the eNOS translocation induced by a [Ca²⁺]i-elevating agonist (10 μM bradykinin). Thus, EPA induces Ca²⁺-independent activation and translocation of eNOS and endothelium-dependent vasorelaxation.

【 授权许可】

Unknown