Dynamics of granzyme B-induced apoptosis: Mathematical modeling

Dynamics of granzyme B-induced apoptosis: Mathematical modeling

Apoptosis is mediated by an intracellular biochemical system that mainly includes proteins (procaspases, caspases, inhibitors, Bcl-2 protein family as well as substances released from mitochondrial intermembrane space). The dynamics of caspase activation and target cleavage in apoptosis induced by g...

Full description

Saved in:
Bibliographic Details
Published in:Mathematical biosciences Vol. 212; no. 1; pp. 54 - 68
Main Authors: Golovchenko, Evdokia N., Hanin, Leonid G., Kaufmann, Scott H., Tyurin, Kirill V., Khanin, Mikhail A.
Format: Journal Article
Language:English
Published: United States Elsevier Inc 01-03-2008
Subjects:
Apoptosis
Apoptosis - physiology
Caspase activation
Granzyme B
Granzymes - physiology
Humans
K562 Cells
Mathematical modeling
Models, Biological
c-IAP1, c-IAP2
Ki-67
DNA-PK
PM-Scl, polymyositis-scleroderma complex
TRAIL
Mi-2
XIAP
PARP-1
TNF
FAK
PMS1, PMS2
Caspase activation
Granzyme B
La
UFD2
IAP
Mathematical modeling
CENP-B
U1
NuMA
ICAD
Apoptosis
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Apoptosis is mediated by an intracellular biochemical system that mainly includes proteins (procaspases, caspases, inhibitors, Bcl-2 protein family as well as substances released from mitochondrial intermembrane space). The dynamics of caspase activation and target cleavage in apoptosis induced by granzyme B in a single K562 cell was studied using a mathematical model of the dynamics of granzyme B-induced apoptosis developed in this work. Also the first application of optimization approach to determination of unknown kinetic constants of biochemical apoptotic reactions was presented. The optimization approach involves solving of two problems: direct and inverse. Solving the direct optimization problem, we obtain the initial (baseline) concentrations of procaspases for known kinetic constants through conditional minimization of a cost function based on the principle of minimum protein consumption by the apoptosis system. The inverse optimization problem is aimed at determination of unknown kinetic constants of apoptotic biochemical reactions proceeding from the condition that the optimal concentrations of procaspases resulting from the solution of the direct optimization problem coincide with the observed ones, that is, those determined by biochemical methods. The Multidimensional Index Method was used to perform numerical solution of the inverse optimization problem.
Bibliography:ObjectType-Article-2
SourceType-Scholarly Journals-1
ObjectType-Feature-1
content type line 23
ISSN:0025-5564
1879-3134
DOI:10.1016/j.mbs.2007.12.002