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Experimental testing of a mathematical model relevant to the extrinsic pathway of apoptosis

Content Provider	Springer Nature Link
Author	Pace, Vincenza Bellizzi, Dina Giorda, Francesca Pan, Maria Luisa Benedictis, Giovanna
Copyright Year	2009
Abstract	Apoptosis is a programmed cell death process, whose complexity led researchers to build mathematical models that could help to identify its crucial steps. In previous works, we theoretically analyzed and numerically simulated a model that describes a pathway from an external stimulus to caspase-3 activation. Here, the results of experiments performed on populations of synchronized cells treated with the inducer Apo2L/TRAIL are reported and are compared with model predictions. In particular, we have compared in vitro and in silico results relevant to the time evolutions of caspase-3 and caspase-8 activities, as well as of the dead cells fractions. In addition, the effect of the BAR gene silencing was evaluated. Caspase-3 activation and cell death is faster in silenced than in nonsilenced cells, thus confirming previous simulation results. Interestingly, Apo2L/TRAIL treatment in itself reduces the BAR gene expression. The qualitative agreement between model predictions and cell cultures behavior suggests that the model captures the essential features of the biological process and could be a tool in further studies of caspases activation. In this manuscript, we report the results of in vitro experiments aimed at revealing the dynamics of caspase activation in a cell population. A qualitative agreement between these results and a mathematical model describing a pathway from an external stimulus to caspase-3 activation was obtained, thus showing that the model captures the essential features of the biological process and may be a reliable tool in further studies of caspase activation.
Starting Page	13
Ending Page	23
Page Count	11
File Format	PDF
ISSN	13558145
Journal	Cell Stress and Chaperones
Volume Number	15
Issue Number	1
e-ISSN	14661268
Language	English
Publisher	Springer Netherlands
Publisher Date	2009-05-20
Publisher Place	Dordrecht
Access Restriction	Subscribed
Subject Keyword	Apoptosis Mathematical model Caspase-3 activation Caspase-8 activation BAR regulation Cancer Research Immunology Biochemistry Cell Biology Biomedicine general
Content Type	Text
Resource Type	Article
Subject	Cell Biology Biochemistry

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