Premium
Activation of calcium‐independent phospholipase A 2 following protease‐activated receptor cleavage in mouse cardiomyocytes
Author(s) -
Sharma Janhavi,
McHowat Jane
Publication year - 2011
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.25.1_supplement.1112.6
Subject(s) - arachidonic acid , thrombin , chemistry , proteases , protease activated receptor , phospholipase c , serine protease , tryptase , phospholipase , receptor , phospholipase a , bradykinin , prostaglandin e2 , phospholipase a2 , medicine , endocrinology , protease , biochemistry , biology , mast cell , platelet , enzyme , immunology
Serine proteases such as thrombin and tryptase can regulate target cells by activating G‐protein coupled protease‐activated receptors (PAR). The role for PAR activation is not well defined and could be pro‐ or anti‐inflammatory. We determined whether activation of calcium‐independent phospholipase A 2 (iPLA 2 ) following PAR cleavage in cardiac myocytes contributes to PAF production and PGE 2 release. We stimulated HL‐1 mouse cardiomyocytes with thrombin or tryptase and measured arachidonic acid and prostaglandin E 2 (PGE 2 ) release, plus platelet‐activating factor (PAF) production. Thrombin (0,1 IU/ml) or tryptase (20 ng/ml) stimulation resulted in a significant increase in arachidonic acid and PGE 2 release that was maximal at 5 mins. Pretreatment of HL‐1 cells with ( R )‐bromoenol lactone (( R )‐BEL), a selective iPLA 2 γ inhibitor, completely blocked thrombin‐ and tryptase‐stimulated arachidonic acid and PGE 2 release. Similarly, increases in PAF production observed in HL‐1 cells stimulated with thrombin (1 IU/ml, 10 mins) or tryptase (20 ng/ml, 10 mins) were inhibited by BEL pretreatment. These data suggest that there is an increase in iPLA 2 γ activity in mouse cardiac myocytes following PAR activation, that results in increased arachidonic acid and PGE 2 release, and increased PAF production, mediators that may play a role in cardiac inflammation.