Bistability analysis of an apoptosis model in the presence of nitric oxide

Abstract

Apoptosis, or programmed cell death, is a normal component of the development and healthy functioning of multicellular organisms. In apoptosis, cells die in response to a variety of stimuli in controlled and regulated ways. The apoptotic pathway is tightly regulated in the cell, since dysregulation of apoptosis may cause various illnesses. Decreased apoptosis induction is implicated in cancer (monostable cell survival) whereas increased apoptosis induction is implicated in neurodegenerative disorders (monostable cell death). In this study, the aim is to perform bistability analysis on the mitochondriadependent apoptosis model under the influence of nitric oxide effects (NO) using Chemical Reaction Network (CRN) analysis. After obtaining ordinary differential equations derived from mass action kinetics, CRN analysis can be performed using a toolbox referred to as CRN Toolbox (CRNT). The model is decomposed into modules, since this toolbox can handle up to 20 complexes. Bistability in the modules is preserved throughout the whole model after the addition of other reactions in the pathway on these modules. Finally, two apoptotic and two cell survival states are obtained depending on the initial conditions in the cell. The results suggest that the anti-apoptotic effect of NO is responsible for the bistable character of the apoptotic pathway..