J. Lipid Res.
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Originally published In Press as doi:10.1194/jlr.M300018-JLR200 on June 16, 2003

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Journal of Lipid Research, Vol. 44, 1686-1691, September 2003
Copyright © 2003 by American Society for Biochemistry and Molecular Biology

Calcium-independent phospholipase A2 mediates CREB phosphorylation in double-stranded RNA-stimulated endothelial cells

Bradley D. Martinson*, Carolyn J. Albert*, John A. Corbett*, Robert B. Wysolmerski{dagger} and David A. Ford1,*

* Departments of Biochemistry and Molecular Biology, St. Louis University, Health Sciences Center, St. Louis, MO 63104
{dagger} Pathology, St. Louis University, Health Sciences Center, St. Louis, MO 63104

1 To whom correspondence should be addressed. e-mail: fordda{at}slu.edu

One of the products of a calcium-independent phospholipase A2 (iPLA2) attack of plasmenylcholine, lysoplasmenylcholine, has previously been shown to activate cAMP-dependent protein kinase (PKA). Because endothelial cells respond to some agonists in part by the activation of iPLA2, the present study was designed to determine whether double-stranded RNA (dsRNA), the primary activator of the antiviral response in endothelial cells, elicits cAMP response element binding protein (CREB) phosphorylation through a mechanism mediated by iPLA2. dsRNA stimulated CREB phosphorylation in bovine pulmonary artery endothelial cells that was inhibited by the iPLA2 inhibitor, bromoenol lactone, and the PKA inhibitor, H-89. Additionally, the product of iPLA2 hydrolysis of plasmenylcholine and lysoplasmenylcholine elicited CREB phosphorylation in bovine pulmonary endothelial cells.

Taken together, the present studies suggest that dsRNA as well as other agonists of endothelial cells elicit signaling mechanisms that include in part CREB phosphorylation mediated by iPLA2.

Abbreviations: BEL, bromoenol lactone; CMC, critical micellar concentration; dsRNA, double-stranded RNA; iPLA2, calcium-independent phospholipase A2; LDH, lactate dehydrogenase; LPS, lipopolysaccharide; pCREB, phospho cAMP response element binding protein; PMA, phorbol myristate acetate; poly IC, polyinosinic-polycytidylic acid

Supplementary key words endothelium • cAMP response element binding protein • cAMP-dependent


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