Important role of energy-dependent mitochondrial pathways in cultured XXXX cardiac myocyte apoptosis.

@entity15622 @entity39 @entity2310 @entity908 @entity5611 @entity4626 @entity205 @entity866 @entity35 @entity4124 @entity413 @entity855
Recent studies have suggested that apoptosis and @entity39 share common features in their signaling pathway and that apoptosis requires intracellular @entity855 for its mitochondrial/ @entity15622 suicide cascade. The present study was, therefore, designed to examine the role of intracellular energy levels in determining the form of cell death in cardiac myocytes. Neonatal @entity35 cardiac myocytes were first incubated for 1 h in @entity413 -free medium containing @entity4626 to achieve metabolic inhibition. The cells were then incubated for another 4 h in similar medium containing @entity866 and graded concentrations of @entity413 to manipulate intracellular @entity855 levels. Under @entity855 -depleting conditions, the cell death caused by @entity866 was primarily @entity39 , as determined by @entity908 kinase release and nuclear staining with @entity5611 homodimer-1. However, under @entity855 -replenishing conditions, @entity866 increased the percentage of apoptotic cells, as determined by nuclear morphology and DNA fragmentation. @entity4124 activation by @entity866 was also @entity855 dependent. However, loss of mitochondrial transmembrane potential (DeltaPsi(m)), @entity2310 translocation, and cytochrome c release were observed in both apoptotic and @entity39 cells. Moreover, @entity205 , an inhibitor of mitochondrial permeability transition, attenuated @entity866 -induced apoptosis and @entity39 through the inhibition of DeltaPsi(m) reduction, cytochrome c release, and @entity4124 activation. Our data therefore suggest that @entity866 induces cell demise through a mitochondrial death signaling pathway and that the presence of intracellular @entity855 favors a shift from @entity39 to apoptosis through caspase activation.
