Cytosolic Phospholipase A2α in Mouse Platelets
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The role of cytosolic phospholipase A2α(cPLA2α) in the release of arachidonic acid (AA) from lipid membranes has been intensely studied , Its ubiquitous expression and precise regulation initially suggested a role in both the regulation of membrane phospholipids and its release, triggered by extracellular signaling, to be converted into potent intracellular and extracellular signaling molecules. The survival of cPLA2α knockout mice, however, suggested that this enzyme has a somewhat redundant role in the upkeep of lipid membranes narrowing its role to its function of providing sharp spikes of intracellular AA to enzymes (cyclooxygenases (COX), lipoxygenases (LOX)), which then produce potent autocrine and/or paracrine lipid mediators upon activation . The multitude of lipid mediators that can be derived from the release of AA makes the study of the precise role of cPLA2α in vivo difficult to dissect. The results, however, of recent studies in knockout mice platelets point to a non-redundant role for cPLA2α in the generation of thromboxane A2 (TXA2) at levels needed to perform a paracrine function, vasoconstriction . These findings provide a basis to understand a number of previous studies in various disease models. Further the separation autocrine and paracrine pathways of TXA2 generation provide a possible explanation for the therapeutic utility of low dose aspirin in the prevention of acute arterial vascular events and insight into the potential of inhibiting this enzyme as therapy for a number of vascular and inflammatory diseases.
KeywordsArachidonic Acid Wildtype Mouse Arachidonic Acid Release Cytosolic Phospholipase Arachidonic Acid Production
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