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Co-induction of cell death and survival pathways by phosphoinositide 3-kinase

Life Sciences
Publication Date
DOI: 10.1016/j.lfs.2005.04.035
  • Phosphoinositide 3-Kinase
  • Reactive Oxygen Species
  • Nf-κB
  • Sapk/Jnk
  • Akt
  • Cell Death
  • Serum Withdrawal


Abstract A single stimulus can induce both the cell death and survival pathway, suggesting that these pathways share common upstream signaling components. In order to define these components, human U937 cells grown in 10% serum were exposed to serum-free media. This treatment resulted in apoptosis, which was found to be mediated by SAPK/JNK. It was previously reported that the serum withdrawal (SW)-induced SAPK activation is mediated by a positive mutual interaction between the reactive oxygen species (ROS) and phosphoinositide 3-kinase (PI3K). This study shows that the ROS/PI3K interaction also induces a NF-κB-dependent survival pathway. Despite the role of PI3K, Akt was found to be irrelevant to the activation of SAPK and NF-κB. Comparative analyses of SAPK and NF-κB for their responses to exogenous H 2O 2 revealed that SAPK activation requires much higher H 2O 2 concentrations than those required for NF-κB activation. Moreover, high lethal concentrations of H 2O 2 were found to activate NF-κB and SAPK in a PI3K-independent manner. These results suggest that ROS induce both the SAPK-dependent apoptotic and NF-κB-mediated survival pathways, and these inducer signals are amplified by PI3K in the SW-triggered pathway. Cell death appears to be favored as this amplification proceeds.

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