Mathematical modeling and sensitivity analysis of the integrated TNF alpha-mediated apoptotic pathway for identifying key regulators
TNF alpha-mediated apoptosis is one of the complex and tightly regulated cellular processes as it involves the activation of both pro- and anti-apoptotic signaling pathways. Thus, it is important to elucidate the molecular players of this process and their dynamics in order to gain an in-depth understanding of the mechanisms underlying apoptosis. To this end, we proposed an integrated model of TNF alpha-mediated apoptosis pathway in Type I cells, formulated based on the principles of mass action kinetics. The model includes major apoptotic modules the extrinsic and intrinsic pathways, the NF kappa B survival signaling and various regulatory mechanisms. We performed simulations and sensitivity analyses to study the role of NF kappa B pathway in regulating apoptosis, and identified IAP as one of the more potent regulators of apoptosis. (C) 2011 Elsevier Ltd. All rights reserved.
mathematical modeling sensitivity analysis apoptosis regulatory mechanisms tnf alpha