Interactions of 12-lipoxygenase with phospholipase A2 isoforms following platelet activation through the glycoprotein VI collagen receptor.
Recent studies implicate the collagen receptor, glycoprotein VI (GPVI) in activation of platelet 12-lipoxygenase (p12-LOX). Herein, we show that GPVI-stimulated 12-hydro(peroxy)eicosatetraenoic acid (H(P)ETE) synthesis is inhibited by palmityl trifluromethyl ketone or oleyloxyethylphosphocholine , but not bromoenol lactone, implicating secretory and cytosolic, but not calcium-independent phospholipase A2 (PLA2) isoforms. Also, following GPVI activation, 12-LOX co-immunoprecipitates with both cytosolic and secretory PLA2 (sPLA2). Finally, venoms containing sPLA2 acutely activate p12-LOX in a dose-dependent manner. This study shows that platelet 12-H(P)ETE generation utilizes arachidonate substrate from both c- and sPLA2 and that 12-LOX functionally associates with both PLA2 isoforms.
Department of Medical Biochemistry and Immunology, Wales College of Medicine, Cardiff University, Heath Park, Cardiff CF14 4XN, UK. coffeymj@cardiff.ac.uk
Marcus J
MJ
Coffey
Barbara
B
Coles
Matthew
M
Locke
Alexandra
A
Bermudez-Fajardo
P Claire
PC
Williams
Gavin E
GE
Jarvis
Valerie B
VB
O'donnell
D001092:Arachidonate 12-Lipoxygenase / Q000378:metabolism*; D001792:Blood Platelets / Q000378:metabolism*; D015153:Blotting, Western; D006801:Humans; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D010741:Phospholipases A / Q000235:genetics / Q000378:metabolism*; D054467:Phospholipases A2; D015539:Platelet Activation; D010980:Platelet Membrane Glycoproteins / Q000378:metabolism*; D011233:Precipitin Tests; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D038981:Receptors, Collagen / Q000378:metabolism*
D007527:Isoenzymes; D010980:Platelet Membrane Glycoproteins; D020033:Protein Isoforms; D038981:Receptors, Collagen; D001092:Arachidonate 12-Lipoxygenase; D010741:Phospholipases A; D054467:Phospholipases A2