Dataset Information

Bagci2006_ApoptoticStimuli

ABSTRACT: This a model from the article: Bistability in apoptosis: roles of bax, bcl-2, and mitochondrial permeability transition pores. Bagci EZ, Vodovotz Y, Billiar TR, Ermentrout GB, Bahar I. Biophys J 2006 Mar 1;90(5):1546-59 16339882 , Abstract: We propose a mathematical model for mitochondria-dependent apoptosis, in which kinetic cooperativity in formation of the apoptosome is a key element ensuring bistability. We examine the role of Bax and Bcl-2 synthesis and degradation rates, as well as the number of mitochondrial permeability transition pores (MPTPs), on the cell response to apoptotic stimuli. Our analysis suggests that cooperative apoptosome formation is a mechanism for inducing bistability, much more robust than that induced by other mechanisms, such as inhibition of caspase-3 by the inhibitor of apoptosis (IAP). Simulations predict a pathological state in which cells will exhibit a monostable cell survival if Bax degradation rate is above a threshold value, or if Bax expression rate is below a threshold value. Otherwise, cell death or survival occur depending on initial caspase-3 levels. We show that high expression rates of Bcl-2 can counteract the effects of Bax. Our simulations also demonstrate a monostable (pathological) apoptotic response if the number of MPTPs exceeds a threshold value. This study supports our contention, based on mathematical modeling, that cooperativity in apoptosome formation is critically important for determining the healthy responses to apoptotic stimuli, and helps define the roles of Bax, Bcl-2, and MPTP vis-a-vis apoptosome formation. This model was taken from the CellML repository and automatically converted to SBML. The original model was: Bagci EZ, Vodovotz Y, Billiar TR, Ermentrout GB, Bahar I. (2006) - version=1.0 The original CellML model was created by: Wendy Kang wkan014@aucklanduni.ac.nz The University of Auckland This model originates from BioModels Database: A Database of Annotated Published Models (http://www.ebi.ac.uk/biomodels/). It is copyright (c) 2005-2011 The BioModels.net Team. To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication for more information. In summary, you are entitled to use this encoded model in absolutely any manner you deem suitable, verbatim, or with modification, alone or embedded it in a larger context, redistribute it, commercially or not, in a restricted way or not.. To cite BioModels Database, please use: Li C, Donizelli M, Rodriguez N, Dharuri H, Endler L, Chelliah V, Li L, He E, Henry A, Stefan MI, Snoep JL, Hucka M, Le Novère N, Laibe C (2010) BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models. BMC Syst Biol., 4:92.

SUBMITTER: Camille Laibe

PROVIDER: MODEL1006230056 | BioModels | 2005-01-01

REPOSITORIES: BioModels

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Dataset's files

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			Action	DRS
	MODEL1006230056?filename=MODEL1006230056-biopax2.owl	Owl
	MODEL1006230056?filename=MODEL1006230056-biopax3.owl	Owl
	MODEL1006230056?filename=MODEL1006230056.m	Other
	MODEL1006230056?filename=MODEL1006230056.pdf	Pdf
	MODEL1006230056?filename=MODEL1006230056.png	Other

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Publications

Bistability in apoptosis: roles of bax, bcl-2, and mitochondrial permeability transition pores.

Bagci E Z EZ Vodovotz Y Y Billiar T R TR Ermentrout G B GB Bahar I I

Biophysical journal 20051209 5

We propose a mathematical model for mitochondria-dependent apoptosis, in which kinetic cooperativity in formation of the apoptosome is a key element ensuring bistability. We examine the role of Bax and Bcl-2 synthesis and degradation rates, as well as the number of mitochondrial permeability transition pores (MPTPs), on the cell response to apoptotic stimuli. Our analysis suggests that cooperative apoptosome formation is a mechanism for inducing bistability, much more robust than that induced by ...[more]

PMID: 16339882

Similar Datasets

Project description:This a model from the article: Computational insights on the competing effects of nitric oxide in regulating apoptosis. Bagci EZ, Vodovotz Y, Billiar TR, Ermentrout B, Bahar I. PLoS One 2008 May 28;3(5):e2249 18509469 , Abstract: Despite the establishment of the important role of nitric oxide (NO) on apoptosis, a molecular-level understanding of the origin of its dichotomous pro- and anti-apoptotic effects has been elusive. We propose a new mathematical model for simulating the effects of nitric oxide (NO) on apoptosis. The new model integrates mitochondria-dependent apoptotic pathways with NO-related reactions, to gain insights into the regulatory effect of the reactive NO species N(2)O(3), non-heme iron nitrosyl species (FeL(n)NO), and peroxynitrite (ONOO(-)). The biochemical pathways of apoptosis coupled with NO-related reactions are described by ordinary differential equations using mass-action kinetics. In the absence of NO, the model predicts either cell survival or apoptosis (a bistable behavior) with shifts in the onset time of apoptotic response depending on the strength of extracellular stimuli. Computations demonstrate that the relative concentrations of anti- and pro-apoptotic reactive NO species, and their interplay with glutathione, determine the net anti- or pro-apoptotic effects at long time points. Interestingly, transient effects on apoptosis are also observed in these simulations, the duration of which may reach up to hours, despite the eventual convergence to an anti-apoptotic state. Our computations point to the importance of precise timing of NO production and external stimulation in determining the eventual pro- or anti-apoptotic role of NO. This model was taken from the CellML repository and automatically converted to SBML. The original model was: Bagci EZ, Vodovotz Y, Billiar TR, Ermentrout B, Bahar I. (2008) - version=1.0 The original CellML model was created by: Wendy Kang wkan014@aucklanduni.ac.nz The University of Auckland This model originates from BioModels Database: A Database of Annotated Published Models (http://www.ebi.ac.uk/biomodels/). It is copyright (c) 2005-2011 The BioModels.net Team. To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication for more information. In summary, you are entitled to use this encoded model in absolutely any manner you deem suitable, verbatim, or with modification, alone or embedded it in a larger context, redistribute it, commercially or not, in a restricted way or not.. To cite BioModels Database, please use: Li C, Donizelli M, Rodriguez N, Dharuri H, Endler L, Chelliah V, Li L, He E, Henry A, Stefan MI, Snoep JL, Hucka M, Le Novère N, Laibe C (2010) BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models. BMC Syst Biol., 4:92.