Co-induction of cell death and survival pathways by phosphoinositide 3-kinase.
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-kappaB-dependent survival pathway. Despite the role of PI3K, Akt was found to be irrelevant to the activation of SAPK and NF-kappaB. Comparative analyses of SAPK and NF-kappaB for their responses to exogenous H(2)O(2) revealed that SAPK activation requires much higher H(2)O(2) concentrations than those required for NF-kappaB activation. Moreover, high lethal concentrations of H(2)O(2) were found to activate NF-kappaB and SAPK in a PI3K-independent manner. These results suggest that ROS induce both the SAPK-dependent apoptotic and NF-kappaB-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.
Lee
Seung Bum
SB
Laboratory of Radiation Tumor Physiology, Korea Institute of Radiological and Medical Sciences, 215-4 Gongneung-dong, Nowon-gu, Seoul 139-706, Korea.
Hong
Sung Hee
SH
Kim
Hoguen
H
Um
Hong-Duck
HD
D015153:Blotting, Western; D020169:Caspases / Q000502:physiology; D016923:Cell Death / Q000502:physiology; D002460:Cell Line; D002470:Cell Survival / Q000502:physiology; D004247:DNA / Q000235:genetics; D024202:Electrophoretic Mobility Shift Assay; D004789:Enzyme Activation / Q000502:physiology; D006801:Humans; D006861:Hydrogen Peroxide / Q000633:toxicity; D020928:Mitogen-Activated Protein Kinases / Q000502:physiology; D016328:NF-kappa B; D051058:Oncogene Protein v-akt / Q000502:physiology; D016877:Oxidants / Q000633:toxicity; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D014162:Transfection
D016328:NF-kappa B; D016877:Oxidants; D017382:Reactive Oxygen Species; D004247:DNA; D006861:Hydrogen Peroxide; D019869:Phosphatidylinositol 3-Kinases; D051058:Oncogene Protein v-akt; D020928:Mitogen-Activated Protein Kinases; D020169:Caspases