Stimulated synthesis of prostaglandin E2 or leukotrien C4 from myocardial cells is not a cause but a result of their injury under hypoxia.
Cardiac muscle cell injury may be related to metabolic changes associated with a rise in intracellular calcium. The mechanisms by which an elevated Ca2+ can cause injury are uncertain, but injury could occur by activation of any one or several calcium-dependent processes. To examine whether the process is mediated by prostaglandins (PG) or leukotriens (LT), we measured the successive release of creatine kinase (CK), PGE2 and LTC4 that have been reported to induce the cell injury via the arachidonic acid cascade, to the culture medium from myocardial cells under hypoxic or aerobic conditions. CK release, a biochemical marker of muscle cell necrosis, was first detected in the medium of hypoxic cultures at 9 h. Both PGE2 and LTC4 production and release were delayed, being first detected at 12 h after initiating hypoxia treatment. Addition of exogenous PGE2 or LTC4 to the culture medium (1.0 or 10 ng/ml) did not cause any effect on the CK release under aerobic condition. Cyclooxygenase inhibitor, indomethacin (1 X 10(-5) M) or lipoxygenase inhibitor, AA861 (1 X 10(-5) M), reduced the synthesis of PGE2 by 80% or LTC4 by 68% under hypoxia, respectively, but caused no beneficial effect on the CK release. These findings suggest that cardiac muscle cells themselves produce PGE2 and LTC4 after hypoxia and that the production of these compounds merely occurs as a result, but not as a cause of cell injury.
D002118:Calcium / Q000502:physiology; D002478:Cells, Cultured; D003402:Creatine Kinase / Q000378:metabolism; D015232:Dinoprostone; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D009124:Muscle Proteins / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism*; D010100:Oxygen; D011458:Prostaglandins E / Q000096:biosynthesis*; D013189:SRS-A / Q000096:biosynthesis*
D009124:Muscle Proteins; D011458:Prostaglandins E; D013189:SRS-A; D003402:Creatine Kinase; D015232:Dinoprostone; D010100:Oxygen; D002118:Calcium; D007213:Indomethacin