title: Death wins against life in a spatially extended model of the caspase-3/8 feedback loop.
abstract: Apoptosis is an important physiological process which enables organisms to remove unwanted or damaged cells. A mathematical model of the extrinsic pro-apoptotic signaling pathway has been introduced by Eissing et al. (2007) and a bistable behavior with a stable death state and a stable life state of the reaction system has been established. In this paper, we consider a spatial extension of the extrinsic pro-apoptotic signaling pathway incorporating diffusion terms and make a model-based, numerical analysis of the apoptotic switch in the spatial dimension. For the parameter regimes under consideration it turns out that for this model diffusion homogenizes rapidly the concentrations which afterward are governed by the original reaction system. The activation of effector-caspase 3 depends on the space averaged initial concentration of pro-caspase 8 and pro-caspase 3 at the beginning of the process.
authors.affiliation: Institute for Analysis, Dynamics and Modeling, University of Stuttgart, Stuttgart, Germany. Markus.Daub@mathematik.uni-stuttgart.de
authors.forename: M
authors.initials: M
authors.lastname: Daub
authors.forename: S
authors.initials: S
authors.lastname: Waldherr
authors.forename: F
authors.initials: F
authors.lastname: Allgöwer
authors.forename: P
authors.initials: P
authors.lastname: Scheurich
authors.forename: G
authors.initials: G
authors.lastname: Schneider
mesh_terms: D017209:Apoptosis / Q000502:physiology*; D020240:Apraxia, Ideomotor; D053148:Caspase 3 / Q000378:metabolism*; D053181:Caspase 8 / Q000378:metabolism*; D025461:Feedback, Physiological; D055641:Mathematical Concepts; D008954:Models, Biological; D015398:Signal Transduction; D049490:Systems Biology
chemical_list: D053148:Caspase 3; D053181:Caspase 8