Martinez-Guimera2017 - Generic negative feedback circuit (Model 4)
This model is described in the article:
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.
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To cite BioModels Database, please use: Chelliah V et al. BioModels: ten-year anniversary. Nucl. Acids Res. 2015, 43(Database issue):D542-8.
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'Molecular habituation' as a potential mechanism of gradual homeostatic loss with age.
- Martinez Guimera A, Welsh CM, Proctor CJ, McArdle A, Shanley DP
- Mechanisms of ageing and development , 1/ 2018 , Volume 169 , pages: 53-62 , PubMed ID: 29146308
- Institute for Cell and Molecular Biosciences (ICaMB), Ageing Research Laboratories, Campus for Ageing and Vitality, Newcastle University, Newcastle Upon Tyne, NE4 5PL,United Kingdom; MRC/Arthritis Research UK Centre for Musculoskeletal Ageing (CIMA), United Kingdom.
- 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.
Submitter of this revision: Alvaro Martinez Guimera
Modellers: Alvaro Martinez Guimera
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- Model originally submitted by : Alvaro Martinez Guimera
- Submitted: Oct 26, 2017 8:51:11 AM
- Last Modified: Dec 5, 2017 5:15:47 PM
Revisions
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Version: 2
- Submitted on: Dec 5, 2017 5:15:47 PM
- Submitted by: Alvaro Martinez Guimera
- With comment: Current version of MODEL1710260003
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Version: 1
- Submitted on: Oct 26, 2017 8:51:11 AM
- Submitted by: Alvaro Martinez Guimera
- With comment: Original import of MODEL1710260003
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