'Molecular habituation' as a potential mechanism of gradual homeostatic loss with age.
'Molecular habituation' as a potential mechanism of gradual homeostatic loss with age.
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DOI：
10.1016/j.mad.2017.11.010
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发表时间：
2018-01
影响因子：
5.3
通讯作者：
Shanley DP
中科院分区：
文献类型：
--
作者：
Martinez Guimera A;Welsh CM;Proctor CJ;McArdle A;Shanley DP
组成性信号表明稳态失调，但它们对信号转导的影响仍然在很大程度上未被探索。采用理论方法来研究氧化应激如何影响氧化还原信号转导。组成信号可以导致干扰信息传输的“分子习惯化”效应。这种理论观察对基本方法的稳健性暗示了这一原则的普遍性。活性氧（ROS）引起分子损伤的能力意味着慢性氧化应激主要是从细胞毒性来源的角度进行研究的。然而，已知的ROS分子作为损伤剂和细胞氧化还原信号的双重性意味着持续氧化应激研究的另一个视角。这是研究氧化应激作为细胞内组成性信号的一个视角。在这项工作中，我们采用了理论的角度作为一种探索性和解释性的方法来研究如何慢性氧化应激可以干扰信号处理的氧化还原信号通路在细胞中。我们报告说，组成信号可以引起一个“分子习惯化”的效果，可以总理逐渐丧失生物功能。这是因为环境中的组成性信号具有通过延长负调节因子的激活来降低信号传导途径的响应性的潜力。此外，我们证明了这种现象是如何可能发生在不同的信号通路暴露于持续的信号，此外在不同层次的生物组织。
Constitutive signals indicate homeostatic dysregulation but their effect on signal transduction remains largely unexplored. A theoretical approach is undertaken to examine how oxidative stress may affect redox signal transduction. Constitutive signals can result in a ‘molecular habituation’ effect that interferes with information transmission. The robustness of such a theoretical observation to the underlying methodology hints at the generality of this principle. The ability of reactive oxygen species (ROS) to cause molecular damage has meant that chronic oxidative stress has been mostly studied from the point of view of being a source of toxicity to the cell. However, the known duality of ROS molecules as both damaging agents and cellular redox signals implies another perspective in the study of sustained oxidative stress. This is a perspective of studying oxidative stress as a constitutive signal within the cell. In this work, we adopt a theoretical perspective as an exploratory and explanatory approach to examine how chronic oxidative stress can interfere with signal processing by redox signalling pathways in the cell. We report that constitutive signals can give rise to a ‘molecular habituation’ effect that can prime for a gradual loss of biological function. This is because a constitutive signal in the environment has the potential to reduce the responsiveness of a signalling pathway through the prolonged activation of negative regulators. Additionally, we demonstrate how this phenomenon is likely to occur in different signalling pathways exposed to persistent signals and furthermore at different levels of biological organisation.
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影响因子：
--
作者：
Besse-Patin A;Estall JL
通讯作者：
Estall JL
影响因子：
4.7
作者：
Decuypere JP;Monaco G;Missiaen L;De Smedt H;Parys JB;Bultynck G
通讯作者：
Bultynck G
影响因子：
3.7
作者：
Faucon PC;Pardee K;Kumar RM;Li H;Loh YH;Wang X
通讯作者：
Wang X
钙和ROS：相互互动。
影响因子：
11.4
作者：
Görlach A;Bertram K;Hudecova S;Krizanova O
通讯作者：
Krizanova O
影响因子：
7.4
作者：
Done, Aaron J.;Gage, Matthew J.;Traustadottir, Tinna
通讯作者：
Traustadottir, Tinna