Md. Jahoor Alam, RK Brojen Singh
Centre for Interdisciplinary Research in Basic Science, Jamia Millia Islamia, New Delhi-110025, India.

ABSTRACT

We study stochastic model of p53-Mdm2 regulatory network in a single cell and allow the cell be in stressed condition by activating the network via Ca ⁺² diffusion. P53 controls the cell cycle arrest and cell apoptosis through interaction with downstream into genes and their signaling pathways. In the present paper, we investigate the impact of calcium signaling on the p53 dynamics via nitric oxide activation. We found that a high level dose of calcium influence drastically the p53-Mdm2 regulation which let the cell in strong stressed condition. Further we found that the increase in calcium level leads to the production of more nitric oxide which influences p53-Mdm2 dynamics. Nitric oxide suppresses the level of Mdm2 protein due to which p53 get more stabilized. These results are supported by various experimental results. We have done simulations both for deterministic as well as stochastic systems to prove these facts. Our results suggest that Ca ⁺² influx in a cell can activate nitric oxide which in turn affecting the p53-Mdm2 pathway. We further investigate how two stressed cells can be coupled via Ca ⁺² diffusive coupling and found that the stressed cells exhibit well synchronization. It reveals that Ca ⁺² influx has two important roles, first activates p53 protein via NO and secondly acts as synchronizing agent. Read more…