Lee Seung Bum, Hong Sung Hee, Kim Hoguen, Um Hong-Duck
Laboratory of Radiation Tumor Physiology, Korea Institute of Radiological and Medical Sciences, 215-4 Gongneung-dong, Nowon-gu, Seoul 139-706, Korea.
Life Sci. 2005 Nov 19;78(1):91-8. doi: 10.1016/j.lfs.2005.04.035. Epub 2005 Sep 12.
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.
单一刺激可诱导细胞死亡和存活途径，这表明这些途径共享共同的上游信号成分。为了确定这些成分，将在10%血清中生长的人U937细胞暴露于无血清培养基中。这种处理导致细胞凋亡，发现其由SAPK/JNK介导。先前有报道称，血清撤除（SW）诱导的SAPK激活是由活性氧（ROS）和磷酸肌醇3激酶（PI3K）之间的正向相互作用介导的。本研究表明，ROS/PI3K相互作用还诱导了一种依赖NF-κB的存活途径。尽管PI3K发挥了作用，但发现Akt与SAPK和NF-κB的激活无关。对SAPK和NF-κB对外源性H₂O₂反应的比较分析表明，SAPK激活所需的H₂O₂浓度远高于NF-κB激活所需的浓度。此外，发现高致死浓度的H₂O₂以不依赖PI3K的方式激活NF-κB和SAPK。这些结果表明，ROS诱导了依赖SAPK的凋亡途径和NF-κB介导的存活途径，并且在SW触发的途径中，这些诱导信号被PI3K放大。随着这种放大的进行，细胞死亡似乎更易发生。
