Turning point in apoptosis/necrosis induced by hydrogen peroxide.
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 microM H2O2 exhibited caspase-9 and caspase-3 activation, finally leading to apoptotic cell death. Treatment with 500 microM 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 microM H2O2, but not with 50 microM 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 microM 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.
Saito
Yoshiro
Y
National Institute of Advanced Industrial Science and Technology (AIST), Human Stress Signal Research Center (HSSRC), Ikeda, Osaka 563 8577, Japan. yoshiro-saito@aist.go.jp
Nishio
Keiko
K
Ogawa
Yoko
Y
Kimata
Junko
J
Kinumi
Tomoya
T
Yoshida
Yasukazu
Y
Noguchi
Noriko
N
Niki
Etsuo
E
D000255:Adenosine Triphosphate / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects*; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D045304:Cytochromes c / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D008928:Mitochondria / Q000378:metabolism; D009336:Necrosis / Q000139:chemically induced; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism
D004791:Enzyme Inhibitors; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D000255:Adenosine Triphosphate; D045304:Cytochromes c; D006861:Hydrogen Peroxide; D011065:Poly(ADP-ribose) Polymerases; D020169:Caspases