Simulating Complex Calcium-Calcineurin Signaling Network

Simulating Complex Calcium-Calcineurin Signaling Network

Model Status

This CellML model runs in both PCEnv and COR to recreate the published results. The units have been checked and they are consistent.

Model Structure

ABSTRACT: Understanding of processes in which calcium signaling is involved is of fundamental importance in systems biology and has many applications in medicine. In this paper we have studied the particular case of the complex calcium-calcineurin-MCIP-NFAT signaling network in cardiac myocytes, the understanding of which is critical for treatment of pathologic hypertrophy and heart failure. By including some most recent experimental findings, we constructed a computational model totally based on biochemical principles. The model can correctly predict the mutant (MCIP1-/-) behavior under different stress such as PO (pressure overload) and CaN* (activated calcineurin) overexpression.

In 2006, Shin et al. published a paper which modelled the dual role of MCIP in cardiac hypertrophy. In the study described here, Cui and Kaandorp have extended this model to include more recent and extensive experimental data. They used Cellerator, an open source software, to automatically generate the equations, and the model was subsequently translated into CellML to facilitate future model exchange, reuse and implementation.

A schematic diagram of the Ca2+-calcineurin-MCIP-NFAT signalling networks in cardiac myocytes described by the model. Abbreviations: calmodulin (CaM); calcineurin (CaN); activated calcineurin (CaN*); nuclear factor of activated T-cells (NFAT); phosphorylated NFAT (NFATP); modulatory calcineurin-interacting protein (MCIP); phosphorylated MCIP on serine 112 (MCIPP); phosphorylated MCIP on both serine 112 and serine 108 (MCIPPP); big mitogen-activated protein kinase 1 (BMK1); glycogen synthase 3β (GSK3β); the complex formed by MCIP and calcineurin (Complex1); the complex formed by MCIPPP and 14-3-3 (Complex2); the complex formed by NFATP and 14-3-3 (Complex3); pressure overload (PO); hypertrophic stimuli (stress).

The original book chapter reference is cited below:

Simulating Complex Calcium-Calcineurin Signaling Network, Jiangjun Cui and Jaap A. Kaandorp, 2008, Lecture Notes in Computer Science, 5013, 110-119, PubMed ID: 16445978.