Koo2013 - Shear stress induced NO production - Model 4

  public model
Model Identifier
BIOMD0000000467
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
BioModels Database MODEL1302180006
BioModels Database BIOMD0000000467
isDescribedBy
PubMed 23708369
hasTaxon
Taxonomy Homo sapiens

Curation status
Curated

Original model(s)
N/A

Tags
Name Description Size Actions

Model files

BIOMD0000000467_url.xml SBML L2V4 representation of Koo2013 - Shear stress induced NO production - Model 4 141.29 KB Preview | Download

Additional files

BIOMD0000000467.vcml Auto-generated VCML file 62.80 KB Preview | Download
BIOMD0000000467-biopax2.owl Auto-generated BioPAX (Level 2) 40.65 KB Preview | Download
BIOMD0000000467-biopax3.owl Auto-generated BioPAX (Level 3) 65.79 KB Preview | Download
BIOMD0000000467.m Auto-generated Octave file 8.52 KB Preview | Download
BIOMD0000000467.sci Auto-generated Scilab file 205.00 bytes Preview | Download
BIOMD0000000467.xpp Auto-generated XPP file 5.55 KB Preview | Download
BIOMD0000000467.pdf Auto-generated PDF file 261.82 KB Preview | Download
BIOMD0000000467.png Auto-generated Reaction graph (PNG) 845.48 KB Preview | Download
BIOMD0000000467.svg Auto-generated Reaction graph (SVG) 87.98 KB Preview | Download
BIOMD0000000467_urn.xml Auto-generated SBML file with URNs 140.58 KB Preview | Download

  • Model originally submitted by : Andrew Koo
  • Submitted: 18-Feb-2013 20:30:04
  • Last Modified: 07-Apr-2014 04:05:10
Revisions
  • Version: 2 public model Download this version
    • Submitted on: 07-Apr-2014 04:05:10
    • Submitted by: Andrew Koo
    • With comment: Current version of Koo2013 - Shear stress induced NO production - Model 4
  • Version: 1 public model Download this version
    • Submitted on: 18-Feb-2013 20:30:04
    • Submitted by: Andrew Koo
    • With comment: Original import of BIOMD0000000467.xml.origin
Legends
: Variable used inside SBML models


Species
Species Initial Concentration/Amount
sa49 degraded 0.0 1E-9*mol
s117 0.0 1E-9*mol
s118 0.0 1E-9*mol
eNOS-CaM-Ca2

calcium(2+) ; Calmodulin-3Calmodulin-1Calmodulin-2
2.12 1E-9*mol
eNOS-Cav-1

Caveolin-1 ; negative regulation of nitric-oxide synthase activity
34.98 1E-9*mol
Calmodulin

Calmodulin-3Calmodulin-1Calmodulin-2
7635.36 1E-9*mol
CaM-Ca2

calcium(2+) ; Calmodulin-3Calmodulin-1Calmodulin-2
347.52 1E-9*mol
Reactions
Reactions Rate Parameters
(eNOS-Cav-1) => (sa49_degraded)

([Caveolin-1; negative regulation of nitric-oxide synthase activity]) => ([sa49_degraded])
kD*s51

kD*[Caveolin-1; negative regulation of nitric-oxide synthase activity]
kD = 9.45E-5 inv_sec
(eNOS-CaM-Ca2) => (s117 + CaM-Ca2)

([calcium(2+); Calmodulin-3Calmodulin-1Calmodulin-2]) => ([s117] + [calcium(2+); Calmodulin-3Calmodulin-1Calmodulin-2])
kD*s50

kD*[calcium(2+); Calmodulin-3Calmodulin-1Calmodulin-2]
kD = 9.45E-5 inv_sec
(Hsp90-p-eNOS) => (s118 + Hsp90)

([Heat shock protein HSP 90-beta; phosphorylated residue]) => ([s118] + [Heat shock protein HSP 90-beta])
kD*s65

kD*[Heat shock protein HSP 90-beta; phosphorylated residue]
kD = 9.45E-5 inv_sec
(CaM-Ca2 + eNOS-Cav-1) => (eNOS-CaM-Ca2)

([calcium(2+); Calmodulin-3Calmodulin-1Calmodulin-2] + [Caveolin-1; negative regulation of nitric-oxide synthase activity]) => ([calcium(2+); Calmodulin-3Calmodulin-1Calmodulin-2])
k3*s51*s48-k3r*s50

k3*[Caveolin-1; negative regulation of nitric-oxide synthase activity]*[calcium(2+); Calmodulin-3Calmodulin-1Calmodulin-2]-k3r*[calcium(2+); Calmodulin-3Calmodulin-1Calmodulin-2]
k3r = 1.5 inv_sec; k3 = 1.5E-4 inv_sec_sub
(CaM-Ca2) => (CaM-Ca4)

([calcium(2+); Calmodulin-3Calmodulin-1Calmodulin-2]) => ([calcium(2+); Calmodulin-3Calmodulin-1Calmodulin-2])
k2*s3*s48-k2r*s47

k2*[calcium(2+); cell]*[calcium(2+); Calmodulin-3Calmodulin-1Calmodulin-2]-k2r*[calcium(2+); Calmodulin-3Calmodulin-1Calmodulin-2]
k2r = 1152.0 inv_sec; k2 = 0.08 inv_sec_sub
(Hsp90-eNOS-CaM-Ca2) => (eNOS-CaM-Ca2 + Hsp90)

([calcium(2+); Heat shock protein HSP 90-beta; Calmodulin-3Calmodulin-1Calmodulin-2]) => ([calcium(2+); Calmodulin-3Calmodulin-1Calmodulin-2] + [Heat shock protein HSP 90-beta])
k7*s61

k7*[calcium(2+); Heat shock protein HSP 90-beta; Calmodulin-3Calmodulin-1Calmodulin-2]
k7 = 1.5 inv_sec
(eNOS-Cav-1 + CaM-Ca4) => (eNOS-CaM-Ca4)

([Caveolin-1; negative regulation of nitric-oxide synthase activity] + [calcium(2+); Calmodulin-3Calmodulin-1Calmodulin-2]) => ([calcium(2+); Calmodulin-3Calmodulin-1Calmodulin-2])
k4*s47*s51

k4*[calcium(2+); Calmodulin-3Calmodulin-1Calmodulin-2]*[Caveolin-1; negative regulation of nitric-oxide synthase activity]
k4 = 0.015 inv_sec_sub
(Hsp90-eNOS) => (eNOS-Cav-1 + Hsp90)

([Heat shock protein HSP 90-beta]) => ([Caveolin-1; negative regulation of nitric-oxide synthase activity] + [Heat shock protein HSP 90-beta])
k7*s66

k7*[Heat shock protein HSP 90-beta]
k7 = 1.5 inv_sec
(Calmodulin) => (CaM-Ca2)

([Calmodulin-3Calmodulin-1Calmodulin-2]) => ([calcium(2+); Calmodulin-3Calmodulin-1Calmodulin-2])
k1*s3*s52-k1r*s48

k1*[calcium(2+); cell]*[Calmodulin-3Calmodulin-1Calmodulin-2]-k1r*[calcium(2+); Calmodulin-3Calmodulin-1Calmodulin-2]
k1 = 0.004 inv_sec_sub; k1r = 10.3 inv_sec
(Hsp90-p-eNOS-CaM-Ca2) => (Hsp90-p-eNOS + CaM-Ca2)

([phosphorylated residue; calcium(2+); Heat shock protein HSP 90-beta; Calmodulin-3Calmodulin-1Calmodulin-2]) => ([Heat shock protein HSP 90-beta; phosphorylated residue] + [calcium(2+); Calmodulin-3Calmodulin-1Calmodulin-2])
k3r*s62-k3*s65*s48

k3r*[phosphorylated residue; calcium(2+); Heat shock protein HSP 90-beta; Calmodulin-3Calmodulin-1Calmodulin-2]-k3*[Heat shock protein HSP 90-beta; phosphorylated residue]*[calcium(2+); Calmodulin-3Calmodulin-1Calmodulin-2]
k3r = 1.5 inv_sec; k3 = 1.5E-4 inv_sec_sub
(Hsp90-eNOS-CaM-Ca2) => (Hsp90 + CaM-Ca2)

([calcium(2+); Heat shock protein HSP 90-beta; Calmodulin-3Calmodulin-1Calmodulin-2]) => ([Heat shock protein HSP 90-beta] + [calcium(2+); Calmodulin-3Calmodulin-1Calmodulin-2])
kD*s61

kD*[calcium(2+); Heat shock protein HSP 90-beta; Calmodulin-3Calmodulin-1Calmodulin-2]
kD = 9.45E-5 inv_sec
(Hsp90-p-eNOS-CaM-Ca2) => (Hsp90 + CaM-Ca2)

([phosphorylated residue; calcium(2+); Heat shock protein HSP 90-beta; Calmodulin-3Calmodulin-1Calmodulin-2]) => ([Heat shock protein HSP 90-beta] + [calcium(2+); Calmodulin-3Calmodulin-1Calmodulin-2])
kD*s62

kD*[phosphorylated residue; calcium(2+); Heat shock protein HSP 90-beta; Calmodulin-3Calmodulin-1Calmodulin-2]
kD = 9.45E-5 inv_sec
Curator's comment:
(added: 19 Aug 2013, 14:10:20, updated: 19 Aug 2013, 14:10:20)
The paper describes four sub-models and an integrated version of the four sub-models. This model corresponds to Model 4 - Shear stress induced NO production. There is no Figure corresponding to this sub-model in the paper. Refer to the integrated model (MODEL1308190000).