Turning point in apoptosis/necrosis induced by hydrogen peroxide.

The turning point between apoptosis and necrosis induced by hydrogen peroxide (H 2 O 2 ) have been investigated using human T-lymphoma Jurkat cells. Cells treated with 50 μM H 2 O 2 exhibited caspase-9 and caspase-3 activation, finally leading to apoptotic cell death. Treatment with 500 μM H 2 O 2 did not exhibit caspase activation and changed the mode of death to necrosis. On the other hand, the release of cytochrome c from the mitochondria was observed under both conditions. Treatment with 500 μM H 2 O 2 , but not with 50 μM H 2 O 2 , caused a marked decrease in the intracellular ATP level; this is essential for apoptosome formation. H 2 O 2 -reducing enzymes such as cellular glutathione peroxidase (cGPx) and catalase, which are important for the activation of caspases, were active under the 500 μM H 2 O 2 condition. Prevention of intracellular ATP loss, which did not influence cytochrome c release, significantly activated caspases, changing the mode of cell death from necrosis to apoptosis. These results suggest that ATP-dependent apoptosome formation determines whether H 2 O 2 -induced cell death is due to apoptosis or necrosis. [ABSTRACT FROM AUTHOR]