The role of oxidative stress in hormesis induced by sodium arsenite in human embryo lung fibroblast (HELF) cellular proliferation model
The role of oxidative stress in hormesis induced by sodium arsenite in human embryo lung fibroblast (HELF) cellular proliferation model
复制标题
氧化应激在亚砷酸钠诱导的人胚肺成纤维细胞（HELF）细胞增殖模型中的毒物兴奋作用中的作用
DOI：
10.1080/15287390701290832
复制
发表时间：
2007-01-01
影响因子：
2.6
通讯作者：
Liu, Qi-Zhan
中科院分区：
文献类型：
--
作者：
Yang, Ping;He, Xiao-Qing;Liu, Qi-Zhan
环境因子诱导的激效剂量-反应关系通常表现为低剂量刺激和高剂量抑制。环境因素诱导的激效机制仍然是一个谜；然而，激效后果可能对健康风险评估产生重大影响。为探讨氧化应激在亚砷酸钠诱导的细胞增殖相关热现象中的作用，测定了不同浓度亚砷酸钠处理不同时间的人胚胎肺成纤维细胞（HELF）的活性氧（ROS）、脂质过氧化（LPO）和热休克蛋白（HSP）水平以及谷胱甘肽过氧化物酶（GSH-Px）和超氧化物歧化酶（SOD）的活性。结果表明，亚砷酸钠在低浓度（0.5 VM作用12、24和48 h）下对细胞增殖有显著的诱导作用，而在高浓度（5和10 μ M作用24和48 h）下对细胞生长有抑制作用，呈0浓度-响应曲线。数据表明，活性氧水平与亚砷酸钠暴露浓度呈正相关。结果表明，高浓度亚砷酸钠可引起LPO损伤。SOD活性在低金属浓度下增强，高金属浓度下抑制，且呈浓度依赖性。同样，热休克蛋白27 （HSP27）水平在低浓度亚砷酸钠的早期暴露时间（3,6和12 h）中升高，但在高浓度亚砷酸钠的暴露时间（24和48 h）中降低。亚砷酸钠在低浓度下降低HSP70的表达，在高浓度下升高HSP70的表达。结果表明，这种由亚砷酸钠诱导的细胞增殖的细胞致热模型发生在HELF细胞中，这可能解释了这种金属的矛盾效应。低浓度亚砷酸钠诱导ROS生成增强，无细胞毒性和细胞保护作用。相反，高浓度亚砷酸钠产生明显的ROS形成、明显的氧化应激和细胞损伤，LPO证明了这一点。
Hormetic dose-response relationships induced by environmental agents are often characterized by a low-dose stimulation and a high-dose inhibition. The mechanisms underlying hormesis induced by environmental agents still remain an enigma; however, hormetic consequences may have significant implications for health risk assessments. To investigate the role of oxidative stress in hormetic phenomena associated with cell proliferation induced by sodium arsenite, the levels of reactive oxygen species (ROS), lipid peroxidation (LPO), and heat-shock proteins (HSP) and the activities of glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) were measured in human embryo lung fibroblast (HELF) cells after treatment with sodium arsenite at various concentrations for differing times. Results showed that sodium arsenite induced significant cell proliferation at low concentrations (0.5 VM for 12, 24, and 48 h), but inhibited cell growth at high amounts (5 and 10 mu M for 24 and 48 h), reflected as a 0 concentration-response curve. Data indicated that the relationship between ROS levels and sodium arsenite exposure concentration displayed a positive correlation. It was found out that sodium arsenite at high concentrations induced LPO damage. The activities of SOD were enhanced at low metal concentrations but inhibited with high amounts in a concentration-dependent manner. Similarly, heat-shock protein 27 (HSP27) levels were increased by sodium arsenite of low concentrations with early exposure time (3, 6, and 12 h), but decreased with high metal concentrations with greater exposure time (24 and 48 h).Sodium arsenite decreased HSP70 expression at lower concentrations, but increased HSP70 expression at higher concentration. The results indicated that this cellular hormetic model of cell proliferation induced by sodium arsenite occurred in HELF cells, which may explain contradictory effects seen with this metal. Sodium arsenite at low concentrations induced enhanced ROS generation without cytotoxicity and a cellular protective effect. In contrast, sodium arsenite at high concentrations produced marked ROS formation, marked oxidative stress, and cellular damage, as evidenced by LPO.