Synchronization in stress p53 network

• Published in: Mathematical medicine and biology 2015-12, Vol.32 (4), p.437-456
• Main Authors: Devi, Gurumayum Reenaroy, Alam, Md Jahoor, Singh, R K Brojen
• Format: Article
• Language: English
• Subjects: Entropy; Humans; Models, Biological; Nitric Oxide - metabolism; Proto-Oncogene Proteins c-mdm2 - metabolism; Stress, Physiological - physiology; Tumor Suppressor Protein p53 - metabolism
• ISSN: 1477-8602
• DOI: 10.1093/imammb/dqv002

We study transition of the temporal behaviours of p53 and MDM2 in a stress p53-MDM2-NO regulatory network induced by a bioactive molecule NO (Nitric Oxide). We further study synchronization among a group of identical stress systems arranged in a 3D array with nearest neighbour diffusive coupling. The role of NO and the effect of noise are investigated. In the single system study, we found three distinct types of temporal behaviour of p53, namely oscillation death, damped oscillation and sustained oscillation, depending on the amount of stress induced by NO, indicating how p53 responds to incoming stress. The correlation among coupled systems increases as the value of the coupling constant (ϵ) is increased (γ increases) and becomes constant after a certain value of ϵ. The permutation entropy spectra H(ϵ) for p53 and MDM2 as a function of ϵ are found to be different due to direct and indirect interaction of NO with respective proteins. We find γ versus ϵ for p53 and MDM2 to be similar in a deterministic approach but different in a stochastic approach, and the separation between γ of the respective proteins as a function of ϵ decreases as system size increases. The role of NO is found to be two-fold: stress induced by NO is prominent at small and large values of ϵ but synchrony induced by it dominates in the moderate range of ϵ. Excess stress induces apoptosis.