Article (Scientific journals)
Bistability analyses of a caspase activation model for receptor-induced apoptosis
Eissing, Thomas; Conzelmann, Holger; Gilles, Ernst Dieter et al.
2004In Journal of Biological Chemistry, 279 (35), p. 36892-36897
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Abstract :
[en] Apoptosis is an important physiological process crucially involved in development and homeostasis of multicellular organisms. Although the major signaling pathways have been unraveled, a detailed mechanistic understanding of the complex underlying network remains elusive. We have translated here the current knowledge of the molecular mechanisms of the death-receptor-activated caspase cascade into a mathematical model. A reduction down to the apoptotic core machinery enables the application of analytical mathematical methods to evaluate the system behavior within a wide range of parameters. Using parameter values from the literature, the model reveals an unstable status of survival indicating the need for further control. Based on recent publications we tested one additional regulatory mechanism at the level of initiator caspase activation and demonstrated that the resulting system displays desired characteristics such as bistability. In addition, the results from our model studies allowed us to reconcile the fast kinetics of caspase 3 activation observed at the single cell level with the much slower kinetics found at the level of a cell population.
Disciplines :
Life sciences: Multidisciplinary, general & others
Author, co-author :
Eissing, Thomas
Conzelmann, Holger
Gilles, Ernst Dieter
Allgöwer, Frank
Bullinger, Eric ;  Université de Liège - ULiège > Dép. d'électric., électron. et informat. (Inst.Montefiore) > Méthodes computationnelles pour la biologie systémique
Scheurich, Peter
Language :
English
Title :
Bistability analyses of a caspase activation model for receptor-induced apoptosis
Publication date :
2004
Journal title :
Journal of Biological Chemistry
ISSN :
0021-9258
eISSN :
1083-351X
Publisher :
American Society for Biochemistry and Molecular Biology, Baltimore, United States - Maryland
Volume :
279
Issue :
35
Pages :
36892-36897
Peer reviewed :
Peer Reviewed verified by ORBi
Available on ORBi :
since 08 May 2009

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