Evidence that cytosolic phospholipase A2 is down‐regulated by protein kinase C in intact human platelets stimulated with fluoroaluminate

FEBS Letters

Nardicchi, Vincenza¹  Nucciarelli, Fabio¹  Porcellati, Serena¹  Gresele, Paolo²  Macchioni, Lara¹  Nenci, Giuseppe G.²  Goracci, Gianfrancesco¹ 

[1] Institute of Medical Biochemistry, University of Perugia, Via del Giochetto, 06100 Perugia, Italy;Institute of Internal and Vascular Medicine, University of Perugia, Via E. Dal Pozzo, 06100 Perugia, Italy

关键词: Phospholipase A2 activation;    Human platelet;    Protein kinase C inhibitors;    Secretory phospholipase A2;    Cytosolic phospholipase A2;    G-protein;    AA;    arachidonic acid;    AACOCF3;    arachidonyltrifluoromethyl ketone;    H-7;    1-(5-isoquinolinylsulfonyl)-2-methylpiperazine;    GF 109203X;    bisindolylmaleimide I;    MAPK;    mitogen-activated protein kinase;    PGI2;    prostacyclin;    PKC;    protein kinase C;    PLC;    phospholipase C;    PMA;    phorbol 12-myristate 13-acetate;    cPLA2;    cytosolic phospholipase A2;    sPLA2;    secretory phospholipase A2;    Thr;    thrombin;    WLP;    washed labelled platelets;   

DOI  :  10.1016/S0014-5793(99)00436-6

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

We reported that protein kinase C (PKC) inhibitors increase the release of arachidonic acid induced by fluoroaluminate (AlF₄ ⁻), an unspecific G-protein activator, in intact human platelets. Now we demonstrate that this effect is independent of the extracellular Ca²⁺ concentration and that AlF₄ ⁻-induced release of AA is abolished by BAPTA, an intracellular Ca²⁺ chelator, even in the presence of GF 109203X, a specific and potent PKC inhibitor. This compound also blocks the liberation of the secretory phospholipase A₂ in the extracellular medium, indicating that this enzyme is not involved in the potentiation of arachidonic acid by PKC inhibitors. On the other hand, the latter effect is completely abolished by treatment of platelets with AACOCF₃, a specific inhibitor of cytosolic phospholipase A₂ (cPLA₂). These observations indicate that cPLA₂ is responsible for the AlF₄ ⁻-induced release of arachidonic acid by a mechanism that is down-regulated by PKC.

【 授权许可】

Unknown