Protease-activated receptor signaling in platelets activates cytosolic phospholipase A2α differently for cyclooxygenase-1 and 12-lipoxygenase catalysis.
Arterioscler Thromb Vasc Biol
; 31(2): 435-42, 2011 Feb.
Article
em En
| MEDLINE
| ID: mdl-21127289
ABSTRACT
OBJECTIVE:
The rate-limiting step in the biosynthesis of thromboxane A(2) (TxA(2)) and 12-hydroxyeicosatetraenoic acid (12-HETE) by platelets is activation of cytosolic phospholipase A(2α) (cPLA(2α)), which releases arachidonic acid, which is the substrate for cyclooxygenase-1 (COX-1) and 12-lipoxygenase. We evaluated signaling via the human platelet thrombin receptors, protease-activated receptor (PAR) 1 and PAR4, to the activation of cPLA(2α), which provides a substrate for the biosynthesis of TxA(2) and 12-HETE. METHODS ANDRESULTS:
Stimulating washed human platelets resulted in delayed biosynthesis of 12-HETE, which continues after maximal formation of TxA(2) is completed, suggesting that 12-HETE is not formed by the same pool of arachidonic acid that provides a substrate to COX-1. PAR1-induced formation of TxA(2) was inhibited by the phosphatidylinositol kinase inhibitor LY294002, whereas this inhibitor did not block 12-HETE biosynthesis. Both 1-butanol and propranolol also blocked TxA(2) biosynthesis but did not inhibit 12-HETE formation.CONCLUSIONS:
The concerted evidence indicates that the platelet thrombin receptors signal activation of cPLA(2α) coupled to COX-1 by a pathway different from that signaling activation of the cPLA(2α) coupled to 12-lipoxygenase.
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Plaquetas
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Araquidonato 12-Lipoxigenase
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Transdução de Sinais
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Citosol
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Receptores Ativados por Proteinase
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Ciclo-Oxigenase 1
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Fosfolipases A2 do Grupo IV
Limite:
Humans
Idioma:
En
Ano de publicação:
2011
Tipo de documento:
Article