Martinez-Guimera2017 - Generic negative feedback circuit (Model 4)

Martinez-Guimera2017 - Generic negative feedback circuit (Model 4)

This model is described in the article:

'Molecular habituation' as a
potential mechanism of gradual homeostatic loss with age.

Martinez Guimera A, Welsh CM,
Proctor CJ, McArdle A, Shanley DP.
Mech. Ageing Dev. 2017 Nov; :
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.

This model is hosted on
BioModels Database
and identified by:
MODEL1710260003.
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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