Premium
12‐Lipoxygenase plays a significant role in regulation of human platelets activation
Author(s) -
Apopa Patrick Leo,
Vesci Joanne,
Boutaud Olivier,
Jadhav Ajit,
Simeonov Anton,
Rai Ganesha,
Maloney David J,
Holman Ted,
Kenyon Victor,
Holinstat Michael
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.574.4
Subject(s) - platelet , lipoxygenase , chemistry , platelet activation , arachidonic acid , dense granule , eicosanoid , biochemistry , stimulation , enzyme , biology , endocrinology , immunology
Platelets play a critical role in both hemostasis and thrombosis. Arachidonic acid (AA), a precursor to eicosanoid formation is one of the polyunsaturated fatty acids found on the platelet cell membrane. Lipoxygenase enzymes metabolize AA to different active metabolites. This study was undertaken to elucidate the effects of Lipoxygenase inhibition on human platelets function. Human platelets were stimulated with different agonists in the presence and absence of a Lipoxygenase‐specific inhibitor. Following stimulation, platelets aggregation and dense granule release was monitored using a lumni‐aggregometer. We show that inhibition of 12‐LOX completely blocks granule release without affecting platelets aggregation. Further analysis showed that 12‐LOX inhibition completely blocked 12‐HETE formation while having only minor effects on TxA 2 levels upon stimulation with different agonists. Flow cytometry assay indicated that the 12‐LOX inhibitor significantly inhibited both GPIIbIIIa activation and α‐granule secretion and biochemical analysis show effects of 12‐LOX inhibition on Rap1 activation. Taken together, these results suggest that 12‐LOX inhibition has the potential of selectively inhibiting 12‐HETE formation and activity without affecting TxA 2 activity and TxA 2 receptor and has the potential to act as an important therapeutic target in the management of thrombosis.