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Selective plasmalogen substrate utilization by thrombin-stimulated Ca(2+)-independent PLA(2) in cardiomyocytes.
1Department of Pathology, St. Louis University School of Medicine, Missouri 63104, USA. mchowatj@slucare1.sluh.edu
Summary
Thrombin activates a calcium-independent phospholipase A(2) (PLA(2)) in heart cells, selectively hydrolyzing specific ether phospholipids. This process releases arachidonic acid, leading to prostacyclin production.
Area of Science:
- Cardiovascular Biology
- Lipid Metabolism
- Enzymology
Background:
- Thrombin is a key enzyme in hemostasis and thrombosis.
- Phospholipase A(2) (PLA(2)) enzymes play critical roles in cellular signaling and inflammation.
- Plasmalogens are ether phospholipids with unique metabolic pathways.
Purpose of the Study:
- To identify endogenous phospholipid substrates of thrombin-stimulated Ca(2+)-independent PLA(2) in rabbit ventricular myocytes.
- To investigate the specific products generated by this enzymatic activity.
- To elucidate the role of this pathway in cellular signaling.
Main Methods:
- Rabbit ventricular myocytes were stimulated with thrombin.
- Quantification of diradyl phospholipid mass, including plasmenylcholine and phosphatidylethanolamine species.
- Measurement of arachidonic acid and lysophospholipid production.
- Analysis of prostacyclin formation.
Main Results:
- Thrombin stimulation selectively decreased arachidonylated plasmenylcholine and plasmenylethanolamine.
- No significant changes were observed in arachidonylated phosphatidylcholine or phosphatidylethanolamine.
- Selective production of lysoplasmenylcholine was detected.
- Released arachidonic acid was rapidly converted to prostacyclin.
Conclusions:
- Thrombin-activated Ca(2+)-independent PLA(2) preferentially hydrolyzes arachidonylated plasmalogens.
- Lysoplasmalogens and prostacyclin are the principal bioactive products of this pathway.
- This pathway may contribute to thrombin-mediated signaling in cardiac cells.