Nitric Oxide as stress inducer and synchronizer of p53 dynamics

TL;DR

This study explores how nitric oxide influences p53 and MDM2 dynamics, revealing stress responses, synchronization behaviors, and the dual role of NO in inducing stress and synchrony within cellular systems.

Contribution

It provides new insights into the effects of NO on p53-MDM2 dynamics, including stress responses, synchronization mechanisms, and the impact of noise and coupling in cellular networks.

Findings

p53 exhibits oscillation death, damped oscillation, and sustained oscillation depending on NO-induced stress.

Synchronization among coupled systems increases with coupling strength and stabilizes after a threshold.

NO has a dual role, inducing stress at low and high coupling, and promoting synchronization at moderate coupling.

Abstract

We study how the temporal behaviours of p53 and MDM2 are affected by stress inducing bioactive molecules NO (Nitric Oxide) in the p53-MDM2-NO regulatory network. We also study synchronization among a group of identical stress systems arranged in a three dimensional array with nearest neighbour diffusive coupling. The role of NO and effect of noise are investigated. In the single system study, we have found three distinct types of temporal behaviour of p53, namely, oscillation death, damped oscillation and sustain oscillation, depending on the amount of stress induced by the NO concentration, indicating how p53 responds to the incoming stress. The correlation among the coupled systems increases as the value of coupling constant (\epsilon) is increased (\gamma increases) and becomes constant after certain value of \epsilon. The permutation entropy spectra H(\epsilon) for p53 and MDM2 as a function of \epsilon are found to be different due to direct and indirect interaction of NO with the respective proteins. \gamma versus \epsilon for p53 and MDM2 are found to be similar in deterministic approach, but different in stochastic approach and the separation between \gamma of the respective proteins as a function of \epsilon decreases as system size increases. The role of NO is found to be twofold: stress induced by it is prominent at small and large values of \epsilon but synchrony inducing by it dominates in moderate range of \epsilon. Excess stress induce apoptosis to the system.