title: Theoretical Analysis of Fas Ligand-Induced Apoptosis with an Ordinary Differential Equation Model.
abstract: Upon the treatment of Fas ligand, different types of cells exhibit different apoptotic mechanisms, which are determined by a complex network of biological pathways. In order to derive a quantitative interpretation of the cell sensitivity and apoptosis pathways, we have developed an ordinary differential equation model. Our model is intended to include all of the known major components in apoptosis pathways mediated by Fas receptor. It is composed of 29 equations using a total of 49 rate constants and 13 protein concentrations. All parameters used in our model were derived through nonlinear fitting to experimentally measured concentrations of four selected proteins in Jurkat T-cells, including caspase-3, caspase-8, caspase-9, and Bid. Our model is able to correctly interpret the role of kinetic parameters and protein concentrations in cell sensitivity to FasL. It reveals the possible reasons for the transition between type-I and type-II pathways and also provides some interesting predictions, such as the more decisive role of Fas over Bax in apoptosis pathway and a possible feedback mechanism between type-I and type-II pathways. But our model failed in predicting FasL-induced apoptotic mechanism of NCI-60 cells from their gene-expression levels. Limitations in our model are also discussed.
authors.affiliation: State Key Laboratory of Bioorganic Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 345 Lingling Road, Shanghai 200032, P. R. China tel: 86-21-54925128.
authors.forename: Zhimin
authors.initials: Z
authors.lastname: Shi
authors.affiliation: State Key Laboratory of Bioorganic Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 345 Lingling Road, Shanghai 200032, P. R. China tel: 86-21-54925128.
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.affiliation: State Key Laboratory of Bioorganic Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 345 Lingling Road, Shanghai 200032, P. R. China tel: 86-21-54925128.
authors.forename: Zhihai
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Shanghai Jiao-Tong University School of Medicine, 227 South Chongqing Road, Shanghai 200025, P. R. China.
authors.forename: Jun
authors.initials: J
authors.lastname: Mi
authors.affiliation: State Key Laboratory of Bioorganic Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 345 Lingling Road, Shanghai 200032, P. R. China tel: 86-21-54925128. wangrx@sioc.ac.cn.
authors.forename: Renxiao
authors.initials: R
authors.lastname: Wang
keywords: Apoptosis pathway; Fas ligand; Ordinary differential equation; Systems biology