Biphasic effect of arsenite on cell proliferation and apoptosis is associated with the activation of JNK and ERK1/2 in human embryo lung fibroblast cells
Biphasic effect of arsenite on cell proliferation and apoptosis is associated with the activation of JNK and ERK1/2 in human embryo lung fibroblast cells
复制标题
亚砷酸盐对细胞增殖和凋亡的双相作用与人胚胎肺成纤维细胞中JNK和ERK1/2的激活有关
DOI：
10.1016/j.taap.2006.12.021
复制
发表时间：
2007-04-01
影响因子：
3.8
通讯作者：
Liu, Qi-Zhan
中科院分区：
文献类型：
--
作者：
He, Xiao-Qing;Chen, Rui;Liu, Qi-Zhan
环境因子诱导的双相剂量-反应关系常表现为低剂量刺激和高剂量抑制效应。一些研究表明，亚砷酸盐可以通过双相剂量-反应关系诱导人类细胞增殖和凋亡，但这种现象背后的机制还不清楚。本研究旨在探讨亚砷酸钠对人胚肺成纤维细胞（HELF）增殖和凋亡的双相效应与JNK和ERK 1/2激活的关系。我们的研究结果表明，细胞增殖可能会刺激在较低浓度（0.1和0.5 μ M）亚砷酸盐，但抑制在较高浓度（5和10 μ M）。以细胞凋亡为终点时，浓度-反应曲线呈U型。在刺激磷酸化JNK水平显着增加，在3，6和12小时后，0.1或0.5 μ M砷暴露。磷酸化ERK 12水平增加与不同浓度（0.1-10 μ M）的亚砷酸盐在6，12，和24小时。用20 μ M SP 600125阻断JNK通路或用100 μ M PD 98059阻断ERK 1/2通路可显著抑制砷对细胞的双相效应。本研究结果提示，INK和ERK 1/2的激活可能参与了亚砷酸盐对HELF细胞增殖和凋亡的双相效应。在双相过程中，INK活化似乎比ERK 1/2活化起更关键的作用。(c)2007年爱思唯尔公司All rights reserved.
Biphasic dose-response relationship induced by environmental agents is often characterized with the effect of low-dose stimulation and high-dose inhibition. Some studies showed that arsenite may induce cell proliferation and apoptosis via biphasic dose-response relationship in human cells; however, mechanisms underlying this phenomenon are not well understood. In the present study, we aimed at investigating the relationship between biphasic effect of arsenite on cell proliferation and apoptosis and activation of JNK and ERK1/2 in human embryo lung fibroblast (HELF) cells. Our results demonstrated that cell proliferation may be stimulated at lower concentrations (0.1 and 0.5 mu M) arsenite but inhibited at higher concentrations (5 and 10 mu M). When cell apoptosis was used as the endpoint, the concentration-response curves were changed to U-shapes. During stimulation phospho-JNK levels were significantly increased at 3, 6, and 12 h after 0.1 or 0.5 mu M arsenite exposure. Phospho-ERK1/2 levels were increased with different concentrations (0.1-10 mu M) of arsenite at 6, 12, and 24 h. Blocking of JNK pathway with 20 mu M SP600125 or ERK1/2 by 100 mu M PD98059 significantly inhibited biphasic effect of arsenite in cells. Data in the present study suggest that activation of INK and ERK1/2 may be involved in biphasic effect of arsenite when measuring cell proliferation and apoptosis in HELF cells. INK activation seems to play a more critical role than ERK1/2 activation in the biphasic process. (c) 2007 Elsevier Inc. All rights reserved.