Release of arachidonate from membrane phospholipids in cultured neonatal rat myocardial cells during adenosine triphosphate depletion. Correlation with the progression of cell injury.

K R Chien; A Sen; R Reynolds; A Chang; Y Kim; M D Gunn; L M Buja; J T Willerson

doi:10.1172/JCI111889

Release of arachidonate from membrane phospholipids in cultured neonatal rat myocardial cells during adenosine triphosphate depletion. Correlation with the progression of cell injury.

K R Chien, A Sen, R Reynolds, A Chang, Y Kim, M D Gunn, L M Buja, and J T Willerson

Published June 1, 1985 - More info

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Abstract

The present study utilized a cultured myocardial cell model to evaluate the relationship between the release of arachidonate from membrane phospholipids, and the progression of cell injury during ATP depletion. High-energy phosphate depletion was induced by incubating cultured neonatal rat myocardial cells with various combinations of metabolic inhibitors (deoxyglucose, oligomycin, cyanide, and iodoacetate). Phospholipid degradation was assessed by the release of radiolabeled arachidonate from membrane phospholipids. In this model, the current study demonstrates that (a) cultured myocardial cells display a time-dependent progression of cell injury during ATP depletion; (b) the morphologic patterns of mild and severe cell injury in the cultured cells are similar to those found in intact ischemic canine myocardial models; (c) cultured myocardial cells release arachidonate from membrane phospholipids during ATP depletion; and (d) using two separate combinations of metabolic inhibitors, there is a correlation between the release of arachidonate, the development of severe cellular and sarcolemmal damage, the release of creatine kinase into the extracellular medium, and the loss of the ability of the myocardial cells to regenerate ATP when the metabolic inhibitors are removed. Thus, the present results suggest that during ATP depletion, in cultured neonatal rat myocardial cells, the release of arachidonate from myocardial membrane phospholipids is linked to the development of membrane defects and the associated loss of cell viability.

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