Koo2013 - Shear stress induced eNOS expression - Model 3

Model Identifier
BIOMD0000000466
Short description
Format
SBML
(L2V4)
Related Publication
-
In silico modeling of shear-stress-induced nitric oxide production in endothelial cells through systems biology.
- Koo A, Nordsletten D, Umeton R, Yankama B, Ayyadurai S, García-Cardeña G, Dewey CF Jr
- Biophysical journal , 5/ 2013 , Volume 104 , pages: 2295-2306 , PubMed ID: 23708369
- Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA.
- Nitric oxide (NO) produced by vascular endothelial cells is a potent vasodilator and an antiinflammatory mediator. Regulating production of endothelial-derived NO is a complex undertaking, involving multiple signaling and genetic pathways that are activated by diverse humoral and biomechanical stimuli. To gain a thorough understanding of the rich diversity of responses observed experimentally, it is necessary to account for an ensemble of these pathways acting simultaneously. In this article, we have assembled four quantitative molecular pathways previously proposed for shear-stress-induced NO production. In these pathways, endothelial NO synthase is activated 1), via calcium release, 2), via phosphorylation reactions, and 3), via enhanced protein expression. To these activation pathways, we have added a fourth, a pathway describing actual NO production from endothelial NO synthase and its various protein partners. These pathways were combined and simulated using CytoSolve, a computational environment for combining independent pathway calculations. The integrated model is able to describe the experimentally observed change in NO production with time after the application of fluid shear stress. This model can also be used to predict the specific effects on the system after interventional pharmacological or genetic changes. Importantly, this model reflects the up-to-date understanding of the NO system, providing a platform upon which information can be aggregated in an additive way.
Contributors
Andrew Koo
Metadata information
is
isDescribedBy
hasTaxon
isVersionOf
Gene Ontology
nitric oxide biosynthetic process
Gene Ontology nitric oxide production involved in inflammatory response
Reactome eNOS synthesizes NO
Gene Ontology response to fluid shear stress
Gene Ontology nitric oxide production involved in inflammatory response
Reactome eNOS synthesizes NO
Gene Ontology response to fluid shear stress
Curation status
Curated
Original model(s)
N/A
Tags
Name | Description | Size | Actions |
---|---|---|---|
Model files |
|||
BIOMD0000000466_url.xml | SBML L2V4 representation of Koo2013 - Shear stress induced eNOS expression - Model 3 | 191.85 KB | Preview | Download |
Additional files |
|||
BIOMD0000000466.m | Auto-generated Octave file | 13.99 KB | Preview | Download |
BIOMD0000000466_urn.xml | Auto-generated SBML file with URNs | 190.76 KB | Preview | Download |
BIOMD0000000466-biopax2.owl | Auto-generated BioPAX (Level 2) | 43.63 KB | Preview | Download |
BIOMD0000000466-biopax3.owl | Auto-generated BioPAX (Level 3) | 69.15 KB | Preview | Download |
BIOMD0000000466.svg | Auto-generated Reaction graph (SVG) | 95.75 KB | Preview | Download |
BIOMD0000000466.pdf | Auto-generated PDF file | 303.27 KB | Preview | Download |
BIOMD0000000466.png | Auto-generated Reaction graph (PNG) | 421.44 KB | Preview | Download |
BIOMD0000000466.xpp | Auto-generated XPP file | 9.68 KB | Preview | Download |
BIOMD0000000466.vcml | Auto-generated VCML file | 86.74 KB | Preview | Download |
BIOMD0000000466.sci | Auto-generated Scilab file | 205.00 Bytes | Preview | Download |
- Model originally submitted by : Andrew Koo
- Submitted: 18-Feb-2013 20:27:51
- Last Modified: 07-Apr-2014 04:00:36
Revisions
-
Version: 2
- Submitted on: 07-Apr-2014 04:00:36
- Submitted by: Andrew Koo
- With comment: Current version of Koo2013 - Shear stress induced eNOS expression - Model 3
-
Version: 1
- Submitted on: 18-Feb-2013 20:27:51
- Submitted by: Andrew Koo
- With comment: Original import of BIOMD0000000466.xml.origin
(*) You might be seeing discontinuous
revisions as only public revisions are displayed here. Any private revisions
of this model will only be shown to the submitter and their collaborators.
Legends
: Variable used inside SBML models
: Variable used inside SBML models
Species
Species | Initial Concentration/Amount |
---|---|
s42 | 50.0 1E-9*mol |
s43 Dual specificity mitogen-activated protein kinase kinase 7 ; phosphorylated residue |
0.006 1E-9*mol |
s44 Mitogen-activated protein kinase 8 ; phosphorylated residue |
0.0 1E-9*mol |
s51 NOS3-201 ; Caveolin-1 |
34.98 1E-9*mol |
s91 SHC-transforming protein 1 |
819.25 1E-9*mol |
s93 Focal adhesion kinase 1 ; phosphorylated residue |
0.605 1E-9*mol |
s95 Focal adhesion kinase 1 |
57.0 1E-9*mol |
s96 Dual specificity mitogen-activated protein kinase kinase 7 |
299.706 1E-9*mol |
s97 Mitogen-activated protein kinase kinase kinase 1 |
98.514 1E-9*mol |
s99 Mitogen-activated protein kinase 8 |
299.997 1E-9*mol |
s100 Dual specificity mitogen-activated protein kinase kinase 7 ; phosphorylated residue |
0.288 1E-9*mol |
s101 Mitogen-activated protein kinase kinase kinase 1 ; phosphorylated residue |
1.486 1E-9*mol |
s102 GTP(3-) ; GTPase HRas |
0.616 1E-9*mol |
Reactions
Reactions | Rate | Parameters |
---|---|---|
s42 => s107; s44, s44, s42 | s44*s42*k21/(Km21+s42) | k21=4.0E-5 inv_sec; Km21=25.0 substance |
s100 => s43; s101, s100, s101 | k15*s100*s101/(Km15+s100) | Km15=15.0 substance; k15=0.005 inv_sec |
s104 => s44; s43, s104, s43 | k19*s104*s43/(Km19+s104) | Km19=30.0 substance; k19=0.002 inv_sec |
s37 => s51; s106, s106 | V27*s106/(s106+Km27) | Km27=16.0 substance; V27=0.02824 nM_inv_s |
s98 => s91; s98 | V8*s98/(Km8+s98) | V8=154.0 nM_inv_s; Km8=340.0 substance |
s95 => s93; s39, s119, s39 | exp(unity-(s39/tf)^0.35)*normal*((s39+tiny_num)/unimol)^-0.65*(unity-(s39/tf)^0.35) | unimol=1.0 substance; normal=4.0 nM_inv_s; tiny_num=1.0E-6 substance; tf=60.0 substance; unity=1.0 dimensionless |
s113 => s114 + s93; s113, s93, s114 | k6*s113-kr6*s93*s114 | k6=2040.0 inv_sec; kr6=15700.0 inv_nM_s |
s100 => s96; s100 | V14*s100/(s100+Km14) | Km14=15.0 substance; V14=0.375 nM_inv_s |
s101 => s97; s101 | V12*s101/(Km12+s101) | V12=0.125 nM_inv_s; Km12=8.0 substance |
s99 => s104; s43, s99, s43 | k17*s99*s43/(s99+Km17) | k17=0.002 inv_sec; Km17=30.0 substance |
s96 => s100; s101, s101, s96 | k13*s101*s96/(Km13+s96) | Km13=15.0 substance; k13=0.005 inv_sec |
s102 => s103; s102 | V10*s102/(Km10+s102) | Km10=0.0571 substance; V10=0.289 nM_inv_s |
Curator's comment:
(added: 19 Aug 2013, 13:57:38, updated: 19 Aug 2013, 13:57:38)
(added: 19 Aug 2013, 13:57:38, updated: 19 Aug 2013, 13:57:38)
The paper describes four sub-models and an integrated version of the four sub-models. This model corresponds to Model 3 - Shear stress induced eNOS expression. Figure 3C of the paper is reproduced here using Copasi 4.10 (Build 55).