Hormesis and Adaptive Cellular Control Systems
Hormesis and Adaptive Cellular Control Systems
复制标题
兴奋效应和自适应细胞控制系统
DOI：
10.2203/dose-response.07-028.zhang
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发表时间：
2008
期刊：
影响因子：
2.5
通讯作者：
M. Andersen
中科院分区：
文献类型：
--
作者：
Qiang Zhang;J. Pi;C. Woods;A. Jarabek;H. Clewell;M. Andersen
许多与生物有机体暴露于环境应激源有关的终点都会发生激素剂量反应。基于细胞的U形或倒U形反应可能来自于参与激活保护细胞免受压力环境所需的适应性反应的常见过程。这些适应性途径扩展了细胞内稳态的区域，并对最终的细胞、器官和系统毒性具有保护作用。然而，应激反应的激活给细胞带来了显著的能量消耗，导致适应或应激细胞中各种基础细胞功能的改变。这种非应激状态和适应状态之间的资源权衡可能导致某些前兆终点的U形或倒U形剂量响应曲线。我们研究这个一般假设与氯，原型氧化应激，使用细胞研究与基因表达分析的反应途径和控制网络的激活与计算建模相结合。离散的细胞状态预期是暴露浓度和持续时间的函数。这些细胞状态包括正常功能状态、轻度至中度暴露时的适应性和应激状态，以及在压倒性浓度的应激源存在下的明显毒性。这些转变可用于改进目前不适应适应性反应的违约风险评估实践。
Hormetic dose response occurs for many endpoints associated with exposures of biological organisms to environmental stressors. Cell-based U- or inverted U-shaped responses may derive from common processes involved in activation of adaptive responses required to protect cells from stressful environments. These adaptive pathways extend the region of cellular homeostasis and are protective against ultimate cell, organ, and system toxicity. However, the activation of stress responses carries a significant energetic cost to the cell, leading to alterations of a variety of basal cellular functions in adapted or stressed cells. This tradeoff of resources between the unstressed and adapted states may lead to U-or inverted U-shaped dose response curves for some precursor endpoints. We examine this general hypothesis with chlorine, a prototype oxidative stressor, using a combination of cellular studies with gene expression analysis of response pathways and with computational modeling of activation of control networks. Discrete cellular states are expected as a function of exposure concentration and duration. These cellular states include normal functioning state, adaptive and stressed states at mild to intermediate exposures, and overt toxicity in the presence of an overwhelming concentration of stressors. These transitions can be used to refine default risk assessment practices that do not currently accommodate adaptive responses.
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影响因子：
7.4
作者：
Pi, Jingbo;Diwan, Bhalchandra A.;Waalkes, Michael P.
通讯作者：
Waalkes, Michael P.
影响因子：
7.4
作者：
Pi, Jingbo;Bai, Yushi;Waalkes, Michael P.
通讯作者：
Waalkes, Michael P.
影响因子：
3.7
作者：
Pi, JB;Qu, W;Waalkes, MP
通讯作者：
Waalkes, MP
DOI：
10.1073/pnas.93.19.10078
发表时间：
1996-09-17
影响因子：
11.1
作者：
Huang, CYF;Ferrell, JE
通讯作者：
Ferrell, JE
影响因子：
3.5
作者：
Lehmler, HJ;Robertson, LW;Kodavanti, PRS
通讯作者：
Kodavanti, PRS