@entity26 deprivation for prolonged periods leads to cardiac cell death and @entity67 . The ability to prevent @entity296 would be of significant therapeutic value in maintaining cardiac function after injury. While caspases have been suggested to play a critical role in apoptosis, their involvement during @entity130 has not been formally determined. In this report, we show that adult ventricular myocytes subjected to @entity519 for 1 h undergo a three-fold increase (P<0.05) in the incidence of apoptosis as determined by TUNEL analysis and @entity2455 nuclear staining. Western blot analysis of @entity519 myocytes revealed a 10-fold increase in the proteolytic processing of @entity522 to @entity14848 with a concomitant cleavage of the @entity522 substrate @entity12982 from 116 kd to @entity8569 kd compared to normoxic controls. Defects in mitochondrial membrane integrity were also observed as evidenced by the translocation of @entity4674 from the mitochondrial to cytosolic compartment of @entity519 cells. Pretreatment of ventricular myocytes with the peptide-caspase inhibitor known to block caspases related to @entity9302 (Ac-YVAD- @entity435 ) attenuated @entity4674 release, processing of @entity522 , and apoptosis. While the caspase inhibitor (Ac-DEVD- @entity435 ) which blocks caspases related to @entity522 , suppressed the cleavage of @entity12982 and apoptosis, it had no effect on @entity4674 release by mitochondria. The data provide direct evidence for the proteolytic activation of caspases during @entity519 -mediated apoptosis of adult ventricular myocytes. Furthermore, the data suggest a hierarchical scheme for caspase activation with mitochondrial @entity4674 release occurring proximally to DEVD- @entity435 -inhibitable caspases.

Caspase activation and mitochondrial XXXX release during @entity519 -mediated apoptosis of adult ventricular myocytes.

@entity296 :: ('MESH:D009202', 'Disease') :: ['myocardial cell death'] @entity522 :: ('836', 'Gene') :: ['caspase 3'] @entity2455 :: ('MESH:D006690', 'Chemical') :: ['Hoechst 33258'] @entity14848 :: ('653820', 'Gene') :: ['p17'] @entity26 :: ('MESH:D010100', 'Chemical') :: ['Oxygen'] @entity4674 :: ('54205', 'Gene') :: ['cytochrome c'] @entity12982 :: ('142', 'Gene') :: ['PARP'] @entity519 :: ('MESH:D000860', 'Disease') :: ['hypoxic', 'hypoxia'] @entity8569 :: ('5296', 'Gene') :: ['p85'] @entity67 :: ('MESH:D018754', 'Disease') :: ['ventricular dysfunction'] @entity435 :: ('CHEBI:42485', 'Chemical') :: ['CHO'] @entity9302 :: ('834', 'Gene') :: ['caspase 1'] @entity130 :: ('MESH:D014947', 'Disease') :: ['hypoxic injury']
@entity4674 :: (54205,Gene) :: ['cytochrome C']
