1. Constitutive activation of AKT pathway inhibits TNF-induced apoptosis in mitochondrial DNA-deficient human myelogenous leukemia ML-1a.
- Author
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Suzuki S, Naito A, Asano T, Evans TT, Reddy SA, and Higuchi M
- Subjects
- Cell Line, Tumor, Chromones pharmacology, Clone Cells, Cycloheximide pharmacology, Humans, Leukemia, Myeloid genetics, Morpholines pharmacology, Phosphoinositide-3 Kinase Inhibitors, Phosphorylation, Signal Transduction, Apoptosis drug effects, DNA, Mitochondrial physiology, Leukemia, Myeloid metabolism, Proto-Oncogene Proteins c-akt metabolism, Tumor Necrosis Factor-alpha pharmacology
- Abstract
TNF plus protein synthesis inhibitor cycloheximide-induced apoptosis in human myelogenous leukemia ML-1a but not in C19, respiration minus mitochondrial DNA-deficient C19 cells, derived from ML-1a. To investigate how mitochondrial DNA depletion inhibits apoptosis, we investigated AKT. Both AKT and its phosphorylated form were observed only in C19, indicating that depletion of mtDNA increased protein and the active form of AKT. Treatment of C19 with LY294002, which inhibits PI-3 kinase and inhibits AKT, significantly increased apoptosis induction by TNF plus cycloheximide and eliminated phosphorylation of AKT. These results indicate that AKT activation was induced by the depletion of mtDNA and inhibited TNF-induced apoptosis.
- Published
- 2008
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