title: PGE2 release from tryptase-stimulated rabbit ventricular myocytes is mediated by calcium-independent phospholipase A2γ.
abstract: Inflammation is associated with cardiovascular disease, including myocardial infarction, atherosclerosis, myocarditis and congestive heart failure. Mast cells have been implicated in inflammation, but their precise role in cardiac inflammation remains unclear. Mast cells contain a variety of pre-formed granule-associated mediators, including tryptase. We have previously demonstrated that the majority of the phospholipase A(2) (PLA(2)) activity in isolated rabbit ventricular myocytes is membrane-associated, calcium-independent and selective for plasmalogen phospholipids. We hypothesized that tryptase stimulation of rabbit ventricular myocytes would increase iPLA(2) activity, leading to increased arachidonic acid and prostaglandin E(2) (PGE(2)) release. Isolated rabbit ventricular myocytes were stimulated with tryptase and iPLA(2) activity, arachidonic acid and PGE(2) release were measured. Tryptase stimulation increased iPLA(2) activity after 5 min. Activation of iPLA(2) was accompanied by increased arachidonic acid and PGE(2) release in tryptase-stimulated myocytes. However no increase in platelet activating factor was observed with tryptase stimulation. To distinguish between different iPLA(2) isoforms in the myocardium, we pretreated ventricular myocytes with the (R)- and (S)-enantiomers of bromoenol lactone (BEL) to selectively inhibit iPLA(2)γ and β respectively. Pretreatment with (R)-BEL resulted in complete inhibition of tryptase-stimulated iPLA(2) activity, arachidonic acid and PGE(2) release, suggesting the iPLA(2)γ is the predominant myocardial isoform activated by tryptase. These studies demonstrate that PGE(2) release from tryptase stimulated rabbit ventricular myocytes is mediated primarily by iPLA(2)γ.
authors: Department of Pathology, Saint Louis University School of Medicine, 1402 S. Grand Blvd., St Louis, MO 63104, USA.
authors: Janhavi
authors: J
authors: Sharma
authors: Jane
authors: J
authors: McHowat
mesh_terms: D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D015232:Dinoprostone / Q000378:metabolism*; D005260:Female; D054513:Group IV Phospholipases A2 / Q000378:metabolism*; D008297:Male; D032383:Myocytes, Cardiac / Q000378:metabolism*; D011817:Rabbits; D053802:Tryptases / Q000378:metabolism*
chemical_list: D016718:Arachidonic Acid; D054513:Group IV Phospholipases A2; D053802:Tryptases; D015232:Dinoprostone; D002118:Calcium