Bagci2006_ApoptoticStimuli

ABSTRACT:

This a model from the article:
Bistability in apoptosis: roles of bax, bcl-2, and mitochondrial permeabilitytransition 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 whichkinetic cooperativity in formation of the apoptosome is a key element ensuringbistability. We examine the role of Bax and Bcl-2 synthesis and degradationrates, as well as the number of mitochondrial permeability transition pores(MPTPs), on the cell response to apoptotic stimuli. Our analysis suggests thatcooperative apoptosome formation is a mechanism for inducing bistability, muchmore robust than that induced by other mechanisms, such as inhibition ofcaspase-3 by the inhibitor of apoptosis (IAP). Simulations predict apathological state in which cells will exhibit a monostable cell survival if Baxdegradation rate is above a threshold value, or if Bax expression rate is belowa threshold value. Otherwise, cell death or survival occur depending on initialcaspase-3 levels. We show that high expression rates of Bcl-2 can counteract theeffects of Bax. Our simulations also demonstrate a monostable (pathological)apoptotic response if the number of MPTPs exceeds a threshold value. This studysupports our contention, based on mathematical modeling, that cooperativity inapoptosome formation is critically important for determining the healthyresponses to apoptotic stimuli, and helps define the roles of Bax, Bcl-2, andMPTP 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
[e-mail]
The University of Auckland

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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.

ORGANISM(S): Homo sapiens

SUBMITTER: Camille Laibe 

PROVIDER: MODEL1006230056 | biostudies-other |

SECONDARY ACCESSION(S): 16339882

REPOSITORIES: biostudies-other