Turning point in apoptosis/necrosis induced by hydrogen peroxide

Abstract

The turning point between apoptosis and necrosis induced by hydrogen peroxide (H₂O₂) have been investigated using human T-lymphoma Jurkat cells. Cells treated with 50 μM H₂O₂ exhibited caspase-9 and caspase-3 activation, finally leading to apoptotic cell death. Treatment with 500 μM H₂O₂ 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 H₂O₂, but not with 50 μM H₂O₂, caused a marked decrease in the intracellular ATP level; this is essential for apoptosome formation. H₂O₂-reducing enzymes such as cellular glutathione peroxidase (cGPx) and catalase, which are important for the activation of caspases, were active under the 500 μM H₂O₂ 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 H₂O₂-induced cell death is due to apoptosis or necrosis.

• Apoptosis
• necrosis
• hydrogen peroxide
• ATP
• oxidative stress
• apoptosome

• 3-ABA
• 3-aminobenzamide
• AcOr
• acridime orange
• Apaf-1
• apoptotic protease activating factor-1
• cGPx
• cellular glutathione peroxidase
• 2D gel
• two-dimentinal gel
• GSH
• glutathione
• H₂O₂
• hydrogen peroxide
• PARP
• poly (ADP-ribose) polymerase
• pI
• isoelectric point
• PI
• propidium iodide
• Prx
• peroxiredoxin
• PS
• phosphatidylserine
• ROS
• reactive oxygen species