Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
2534740 | European Journal of Pharmacology | 2008 | 9 Pages |
Abruquinone A, a natural isoflavanquinone, suppressed A23187- and formyl-Met-Leu-Phe (fMLP)-induced production of thromboxane B2 and leukotriene B4 from rat neutrophils. This compound failed to inhibit the enzymatic activity of ram seminal vesicles cyclooxygenase (COX) and human recombinant 5-lipoxygenase (5-LO) in cell-free systems. Abruquinone A diminished the arachidonic acid release from [3H]arachidonic acid-loaded neutrophils stimulated with either fMLP or A23187, whereas it had no inhibitory effect on the cytosolic phospholipase A2 (cPLA2) activity of neutrophil cytosolic fraction. Based on the Western blot analysis, the nuclear membrane recruitment of cPLA2 and 5-LO was inhibited by abruquinone A in A23187- as well as in fMLP-stimulated cells. Moreover, the phosphorylation of both cPLA2 and extracellular signal regulated kinases (ERKs) induced by fMLP and A23187 was attenuated by abruquinone A in a parallel concentration-dependent manner. Abruquinone A attenuated both fMLP- and ionomycin-mediated [Ca2+]i elevation in a concentration range that inhibited the recruitment of cPLA2 to nuclear membrane. These results indicate that the blockade of leukotriene B4 production by abruquinone A implicates the attenuation of 5-LO membrane translocation. Inhibition of thromboxane B2 production by abruquinone A is due to the attenuation of cPLA2 membrane recruitment and/or cPLA2 phosphorylation through the blockade of [Ca2+]i elevation and ERK activation, respectively.