Boswellic acids stimulate arachidonic acid release and 12-lipoxygenase activity in human platelets independent of Ca2+ and differentially interact with platelet-type 12-lipoxygenase

摘要: Boswellic acids inhibit the transformation of arachidonic acid to leukotrienes via 5-lipoxygenase but can also enhance liberation in human leukocytes and platelets. Using platelets, we explored molecular mechanisms underlying boswellic acid-induced release subsequent metabolism by platelet-type 12-li-poxygenase (p12-LO). Both beta-boswellic 3-O-acetyl-11-keto-boswellic (AKBA) markedly enhanced cytosolic phospholipase A2 (cPLA2), whereas for generation 12-hydro(pero)xyeicosatetraenoic [12-H(P)ETE], AKBA was less potent than without effect at higher concentrations (> or =30 microM). In contrast thrombin, ara-chidonic formation 12-H(P)ETE more rapid occurred absence Ca2+. The Ca2+-independent production elicited not affected pharmacological inhibitors signaling molecules relevant agonist-induced metabolism. It is noteworthy that cell-free assays, increased p12-LO catalysis approximately 2-fold presence Ca2+, inhibited activity. No direct modulatory effects on cPLA2 activity assays were evident. Therefore, immobilized KBA (linked Sepharose beads) selectively precipitated from platelet lysates failed bind cPLA2. Taken together, show induce synthesis platelets unique routes, identified as a selective target acids.