Abstract
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.
Highlights
Whilst reactive oxygen species (ROS) are known to be deleterious and unavoidable products of cellular metabolism, it is apparent that these molecules mediate essential signalling functions within cells (Winterbourn, 2015; Wang and Hai, 2016)
This is significant since the negative regulator in Model 3 is independent of the levels of the ‘Activator’ molecule suggesting the reduced sensitivity could stem from a reduced signal processing at the level of the activator
Ageing and disease can be understood as a loss of biological homeostasis
Summary
Whilst reactive oxygen species (ROS) are known to be deleterious and unavoidable products of cellular metabolism, it is apparent that these molecules mediate essential signalling functions within cells (Winterbourn, 2015; Wang and Hai, 2016). The elucidation of redox signalling pathways occurred in parallel to the accumulation of evidence that various tissues displayed markers of oxidative stress in various pathologies (Besse-Patin and Estall, 2014; Barbieri and Sestili, 2012; De Marchi et al, 2013; Kim et al, 2015; Sosa et al, 2013; Brioche and Lemoine-Morel, 2016; Lepetsos and Papavassiliou, 2016) and the ageing process (Sanz, 2016; Kirkwood and Kowald, 2012). Constitutive oxidative stress is associated with a prolonged state of elevated oxidant levels. Oxidative stress has drawn considerable attention due to the intrinsic reactivity of ROS (Winterbourn, 2015). This chemical property confers these molecules the capacity to cause molecular damage, flagging them as potential causal agents of observed homeostatic disruptions in age and disease
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