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Interactions of 12‐lipoxygenase with phospholipase A 2 isoforms following platelet activation through the glycoprotein VI collagen receptor
Author(s) -
Coffey Marcus J.,
Coles Barbara,
Locke Matthew,
Bermudez-Fajardo Alexandra,
Williams P.Claire,
Jarvis Gavin E.,
O'Donnell Valerie B.
Publication year - 2004
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2004.09.007
Subject(s) - gpvi , gene isoform , phospholipase a2 , biochemistry , chemistry , platelet , cytosol , platelet activation , receptor , lipoxygenase , phospholipase c , glycoprotein , phospholipase a , arachidonic acid , isozyme , microbiology and biotechnology , enzyme , platelet membrane glycoprotein , biology , immunology , gene
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 A 2 (PLA 2 ) isoforms. Also, following GPVI activation, 12‐LOX co‐immunoprecipitates with both cytosolic and secretory PLA 2 (sPLA 2 ). Finally, venoms containing sPLA 2 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 sPLA 2 and that 12‐LOX functionally associates with both PLA 2 isoforms.