Correlation of oxidant-induced acute ATP depletion with delayed cell death in human neuroblastoma cells.
We correlated the adenine nucleotide (AN) levels and energy charge (EC) at the end of a transient oxidative exposure to the delayed death of neuronal cells. When wild-type (WT) or Bcl-2-overexpressing (BCL-2) human neuroblastoma cells (Paju) were exposed to 250 microM H(2)O(2) for 60 min, the EC of WT cells was unchanged, but that of BCL-2 cells decreased from 0.91 +/- 0.03 to 0.67 +/- 0.02. Depletion of ANs was significantly greater in BCL-2 (66.7 +/- 2%) than in WT (38.8 +/- 2%) cells. Proliferation of both lines decreased, averaging 63 +/- 17% of control by 48 h. Exposure to 5 mM H(2)O(2) caused no further change in ANs in BCL-2 cells but in WT cells decreased the EC to 0.45 +/- 0.08 and depleted ANs to 41 +/- 9% of control; after 24 h, WT cells became pyknotic and showed DNA fragmentation but no chromatin condensation, whereas BCL-2 cells died by delayed necrosis. After 10 mM H(2)O(2), EC dropped to 0.15 +/- 0.1, and both lines were acutely killed. The EC after an oxidative insult correlated well with further growth of both cell lines. A significant decline in EC led to delayed death. Bcl-2 did not protect against the fall in EC or AN depletion, but, although survival was not improved, the mechanism of death appeared to be different.
Aito
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Hospital for Children and Adolescents, FIN-00029 Helsinki, Finland. henrikka.aito.huch.fi
Aalto
T K
TK
Raivio
K O
KO
D000225:Adenine / Q000493:pharmacokinetics; D000255:Adenosine Triphosphate / Q000378:metabolism*; D002250:Carbon Radioisotopes; D002452:Cell Count; D016923:Cell Death / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004734:Energy Metabolism / Q000187:drug effects; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D009447:Neuroblastoma; D009474:Neurons / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D016877:Oxidants / Q000494:pharmacology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism
D002250:Carbon Radioisotopes; D016877:Oxidants; D019253:Proto-Oncogene Proteins c-bcl-2; D000255:Adenosine Triphosphate; D006861:Hydrogen Peroxide; D000225:Adenine