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BIOMD0000000344 - Proctor2011_ProteinHomeostasis_NormalCondition

 

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Reference Publication
Publication ID: 21779370
Proctor CJ, Lorimer IA.
Modelling the role of the Hsp70/Hsp90 system in the maintenance of protein homeostasis.
PLoS ONE 2011; 6(7): e22038
Centre for Integrated Systems Biology of Ageing and Nutrition, Institute for Ageing and Health, Newcastle University, Newcastle upon Tyne, United Kingdom. c.j.proctor@ncl.ac.uk  [more]
Model
Original Model: Proctor_chaperone
Submitter: Carole Proctor
Submission ID: MODEL1005280000
Submission Date: 28 May 2010 10:45:33 UTC
Last Modification Date: 25 Feb 2015 12:50:06 UTC
Creation Date: 21 Jul 2011 16:40:43 UTC
Encoders:  Vijayalakshmi Chelliah
   Carole J Proctor
set #1
bqbiol:hasProperty Human Disease Ontology neurodegenerative disease
set #2
bqmodel:isDerivedFrom BioModels Database Proctor2005 - Actions of chaperones and their role in ageing
set #3
bqbiol:hasProperty Mathematical Modelling Ontology MAMO_0000046
set #4
bqbiol:hasTaxon Taxonomy Chordata
set #5
bqbiol:isVersionOf Gene Ontology chaperone mediated protein folding requiring cofactor
Gene Ontology heat shock protein activity
Gene Ontology apoptotic process
Gene Ontology inclusion body assembly
Notes

This model is from the article:
Modelling the Role of the Hsp70/Hsp90 System in the Maintenance of Protein Homeostasis
Proctor CJ, Lorimer IAJ PLoS ONE2011; 6(7): e22038. doi:10.1371/journal.pone.0022038,
Abstract:
Neurodegeneration is an age-related disorder which is characterised by the accumulation of aggregated protein and neuronal cell death. There are many different neurodegenerative diseases which are classified according to the specific proteins involved and the regions of the brain which are affected. Despite individual differences, there are common mechanisms at the sub-cellular level leading to loss of protein homeostasis. The two central systems in protein homeostasis are the chaperone system, which promotes correct protein folding, and the cellular proteolytic system, which degrades misfolded or damaged proteins. Since these systems and their interactions are very complex, we use mathematical modelling to aid understanding of the processes involved. The model developed in this study focuses on the role of Hsp70 (IPR00103) and Hsp90 (IPR001404) chaperones in preventing both protein aggregation and cell death. Simulations were performed under three different conditions: no stress; transient stress due to an increase in reactive oxygen species; and high stress due to sustained increases in reactive oxygen species. The model predicts that protein homeostasis can be maintained during short periods of stress. However, under long periods of stress, the chaperone system becomes overwhelmed and the probability of cell death pathways being activated increases. Simulations were also run in which cell death mediated by the JNK (P45983) and p38 (Q16539) pathways was inhibited. The model predicts that inhibiting either or both of these pathways may delay cell death but does not stop the aggregation process and that eventually cells die due to aggregated protein inhibiting proteasomal function. This problem can be overcome if the sequestration of aggregated protein into inclusion bodies is enhanced. This model predicts responses to reactive oxygen species-mediated stress that are consistent with currently available experimental data. The model can be used to assess specific interventions to reduce cell death due to impaired protein homeostasis.

Note:

Simulations were performed under three different conditions: 1) normal condition (no stress), 2) moderate stress due to an increase in reactive oxygen species (ROS) i.e. ROS levels were increased by a factor of 4 at time=4hours for a period of 1 hour (not 2 hours as mentioned in the figure 5 legend of the reference publication. This is a typo in the paper and is clarified by the author) and 3) high stress due to sustained increase in reactive oxygen species (ROS) (here ROS increases with time).

The model that corresponds to the normal condition is submitted as a main model in the BioModels Database. The other two models, that corresponds to the moderate stress conditions and high stress conditions are available in SBML format as supporting files [go to Curation tab].

Supplementary figures S3 (normal condition), S4 (moderate stress condition) and S6 (high stress condition) are reproduced here.

Model
Publication ID: 21779370 Submission Date: 28 May 2010 10:45:33 UTC Last Modification Date: 25 Feb 2015 12:50:06 UTC Creation Date: 21 Jul 2011 16:40:43 UTC
Mathematical expressions
Reactions
ProteinSynthesis Misfolding Hsp90MisPBinding Hsp90unsuccessulRefolding
Hsp90refolding Hsp70MisPBinding Hsp70unsuccessulRefolding Hsp70refolding
Hsp70ClientBinding Hsp70ClientRelease Hsp90ClientBinding Hsp90ClientRelease
Hsp90HSF1Binding Hsp90HSF1Release dimerisation trimerisation
deTrimerisation deDimerisation HSE70TriHBinding HSE70TriHRelease
HSE90TriHBinding HSE90TriHRelease Hsf1_Hsf1_Hsf1Phosphorylation Hsf1_Hsf1_Hsf1DePhosphorylation
HSE70PhosTriHBinding HSE70PhosTriHRelease HSE90PhosTriHBinding HSE90PhosTriHRelease
Hsp90BasalSynthesis Hsp90Upregulation Hsp90ProteasomeBinding Hsp90Degradation
Hsp70BasalSynthesis Hsp70Upregulation Hsp70ProteasomeBinding Hsp70Degradation
MisPProteasomeBinding1 MisPProteasomeBinding2 MisPDegradation radicalFormation
radicalScavenging Hsp70_PpxBinding Hsp70_PPXRelease JnkPhosphorylation
JNKDephosphorylatioByMkp1 p38Phosphorylation p38DePhosphorylationByMkp1 Aggregation1
SequesteringOfAggregate InclusionGrowth ProteasomeInhibtion ROSgenerationSmallAggP
ROSgenerationAggPProteasome AktSynthesis Hsp90AktBinding Hsp90AktRelease
CHIPbinding CHIPrelease AktProteasomeBinding AktProteasomeRelease
AktDegradation Mkp1Synthesis Mkp1ProteasomeBinding Mkp1Degradation
Mkp1Phosphorylation Mkp1Dephosphorylation p38ROSproduction Hsp70Damage
Hsp90Damage Hsp70DamProteasomeBinding Hsp90DamProteasomeBinding Hsp70DamAggregation1
Hsp70DamInclusionFormation Hsp90DamAggregation Hsp90DamInclusionFormation Hsp70DamSequestering
Hsp90DamSequestering p38CellDeath JnkCellDeath PICellDeath
Rules
Assignment Rule (variable: tot_Hsp90) Assignment Rule (variable: tot_Hsp70) Assignment Rule (variable: tot_MisP)  
Events
DeathOfCell      
Physical entities
Compartments Species
cytosol NatP MisP Hsp70
Hsp90 Hsp70_dam Hsp90_dam
Hsp90_Proteasome Hsp70_Proteasome Hsp70Client
Hsp90Client Hsp70_Hsp70Client Hsp90_Hsp90Client
Akt Akt_Hsp90 CHIP
Akt_CHIP_Hsp90 Akt_Proteasome Hsf1
Hsf1_Hsp90 Hsp90_MisP Hsp70_MisP
Hsf1_Hsf1 Jnk Jnk_P
Ppx Mkp1 Mkp1_P
Mkp1_Proteasome Hsp70_Ppx Pkc
p38 p38_P Proteasome
MisP_Proteasome AggP SeqAggP
AggP_Proteasome ROS ATP
ADP Source Sink
p38Death JNKDeath PIDeath
CellDeath    
nucleus Hsf1_Hsf1_Hsf1 Hsf1_Hsf1_Hsf1_P HSEHsp70
HSEHsp90 HSEHsp70_Hsf1_Hsf1_Hsf1 HSEHsp70_Hsf1_Hsf1_Hsf1_P
HSEHsp90_Hsf1_Hsf1_Hsf1 HSEHsp90_Hsf1_Hsf1_Hsf1_P  
Global parameters
ksynNatP kmisfold kbinMisPProt kdegMisP
kagg kseqagg kbinAggPProt kbinHspMisp
krelHspMisp krefold kbinHsf1Hsp90 krelHsf1Hsp90
kdimerHsf1 ktrimerHsf1 kdetrimerHsf1 kdedimerHsf1
kbinHSEHsf1 krelHSEHsf1 kupregHsp kbasalsynHsp70
kbasalsynHsp90 kbinHsp70Prot kbinHsp90Prot kdegHsp70
kdegHsp90 kgenROS kremROS kbinHsp70client
krelHsp70client kbinHsp90client krelHsp90client kphosJnk
kdephosJnkMkp1 kbinHsp70Ppx krelHsp70Ppx kphosHsf1
kdephosHsf1 kbinHSEPhosTriH krelHSEPhosTriH kphosp38
kdephosp38Mkp1 kgenROSAggP ksynAkt kbinAktHsp90
krelAktHsp90 kbinAktProt krelAktProt kdegAkt
kbinCHIP krelCHIP ksynMkp1 kbinMkp1Prot
kdegMkp1 kphosMkp1 kdephosMkp1 kgenROSp38
kdamHsp kp38death kJnkdeath kPIdeath
kp38act kalive tot_Hsp90 tot_Hsp70
tot_MisP      
Reactions (80)
 
 ProteinSynthesis [Source] → [NatP];  
 
 Misfolding [NatP] + [ROS] → [MisP] + [ROS];  
 
 Hsp90MisPBinding [MisP] + [Hsp90] → [Hsp90_MisP];  
 
 Hsp90unsuccessulRefolding [Hsp90_MisP] → [MisP] + [Hsp90];  
 
 Hsp90refolding [Hsp90_MisP] + [ATP] → [Hsp90] + [NatP] + [ADP];  
 
 Hsp70MisPBinding [MisP] + [Hsp70] → [Hsp70_MisP];  
 
 Hsp70unsuccessulRefolding [Hsp70_MisP] → [MisP] + [Hsp70];  
 
 Hsp70refolding [Hsp70_MisP] + [ATP] → [Hsp70] + [NatP] + [ADP];  
 
 Hsp70ClientBinding [Hsp70] + [Hsp70Client] → [Hsp70_Hsp70Client];  
 
 Hsp70ClientRelease [Hsp70_Hsp70Client] → [Hsp70] + [Hsp70Client];  
 
 Hsp90ClientBinding [Hsp90] + [Hsp90Client] → [Hsp90_Hsp90Client];  
 
 Hsp90ClientRelease [Hsp90_Hsp90Client] → [Hsp90] + [Hsp90Client];  
 
 Hsp90HSF1Binding [Hsp90] + [Hsf1] → [Hsf1_Hsp90];  
 
 Hsp90HSF1Release [Hsf1_Hsp90] → [Hsp90] + [Hsf1];  
 
 dimerisation 2.0 × [Hsf1] → [Hsf1_Hsf1];  
 
 trimerisation [Hsf1] + [Hsf1_Hsf1] → [Hsf1_Hsf1_Hsf1];  
 
 deTrimerisation [Hsf1_Hsf1_Hsf1] → [Hsf1] + [Hsf1_Hsf1];  
 
 deDimerisation [Hsf1_Hsf1] → 2.0 × [Hsf1];  
 
 HSE70TriHBinding [Hsf1_Hsf1_Hsf1] + [HSEHsp70] → [HSEHsp70_Hsf1_Hsf1_Hsf1];  
 
 HSE70TriHRelease [HSEHsp70_Hsf1_Hsf1_Hsf1] → [HSEHsp70] + [Hsf1_Hsf1_Hsf1];  
 
 HSE90TriHBinding [Hsf1_Hsf1_Hsf1] + [HSEHsp90] → [HSEHsp90_Hsf1_Hsf1_Hsf1];  
 
 HSE90TriHRelease [HSEHsp90_Hsf1_Hsf1_Hsf1] → [HSEHsp90] + [Hsf1_Hsf1_Hsf1];  
 
 Hsf1_Hsf1_Hsf1Phosphorylation [Hsf1_Hsf1_Hsf1] + [Pkc] → [Hsf1_Hsf1_Hsf1_P] + [Pkc];  
 
 Hsf1_Hsf1_Hsf1DePhosphorylation [Hsf1_Hsf1_Hsf1_P] + [Hsp70_Ppx] → [Hsf1_Hsf1_Hsf1] + [Hsp70_Ppx];  
 
 HSE70PhosTriHBinding [Hsf1_Hsf1_Hsf1_P] + [HSEHsp70] → [HSEHsp70_Hsf1_Hsf1_Hsf1_P];  
 
 HSE70PhosTriHRelease [HSEHsp70_Hsf1_Hsf1_Hsf1_P] → [Hsf1_Hsf1_Hsf1_P] + [HSEHsp70];  
 
 HSE90PhosTriHBinding [Hsf1_Hsf1_Hsf1_P] + [HSEHsp90] → [HSEHsp90_Hsf1_Hsf1_Hsf1_P];  
 
 HSE90PhosTriHRelease [HSEHsp90_Hsf1_Hsf1_Hsf1_P] → [Hsf1_Hsf1_Hsf1_P] + [HSEHsp90];  
 
 Hsp90BasalSynthesis [Source] → [Hsp90];  
 
 Hsp90Upregulation [HSEHsp90_Hsf1_Hsf1_Hsf1_P] → [HSEHsp90_Hsf1_Hsf1_Hsf1_P] + [Hsp90];  
 
 Hsp90ProteasomeBinding [Hsp90] + [Proteasome] → [Hsp90_Proteasome];  
 
 Hsp90Degradation [Hsp90_Proteasome] + [ATP] → [Proteasome] + [ADP];  
 
 Hsp70BasalSynthesis [Source] → [Hsp70];  
 
 Hsp70Upregulation [HSEHsp70_Hsf1_Hsf1_Hsf1_P] → [HSEHsp70_Hsf1_Hsf1_Hsf1_P] + [Hsp70];  
 
 Hsp70ProteasomeBinding [Hsp70] + [Proteasome] → [Hsp70_Proteasome];  
 
 Hsp70Degradation [Hsp70_Proteasome] + [ATP] → [Proteasome] + [ADP];  
 
 MisPProteasomeBinding1 [Hsp70_MisP] + [Proteasome] → [MisP_Proteasome] + [Hsp70];  
 
 MisPProteasomeBinding2 [Hsp90_MisP] + [Proteasome] → [MisP_Proteasome] + [Hsp90];  
 
 MisPDegradation [MisP_Proteasome] + [ATP] → [Proteasome] + [ADP];  
 
 radicalFormation [Source] → [ROS];  
 
 radicalScavenging [ROS] → [Sink];  
 
 Hsp70_PpxBinding [Hsp70] + [Ppx] → [Hsp70_Ppx];  
 
 Hsp70_PPXRelease [Hsp70_Ppx] → [Hsp70] + [Ppx];  
 
 JnkPhosphorylation [ROS] + [Jnk] → [ROS] + [Jnk_P];  
 
 JNKDephosphorylatioByMkp1 [Jnk_P] + [Mkp1_P] → [Jnk] + [Mkp1_P];  
 
 p38Phosphorylation [ROS] + [p38] → [ROS] + [p38_P];  
 
 p38DePhosphorylationByMkp1 [p38_P] + [Mkp1_P] → [p38] + [Mkp1_P];  
 
 Aggregation1 2.0 × [MisP] → [AggP];  
 
 SequesteringOfAggregate [MisP] + [AggP] → [SeqAggP];  
 
 InclusionGrowth [SeqAggP] + [MisP] → 2.0 × [SeqAggP];  
 
 ProteasomeInhibtion [AggP] + [Proteasome] → [AggP_Proteasome];  
 
 ROSgenerationSmallAggP [AggP] → [AggP] + [ROS];  
 
 ROSgenerationAggPProteasome [AggP_Proteasome] → [AggP_Proteasome] + [ROS];  
 
 AktSynthesis [Source] → [Akt];  
 
 Hsp90AktBinding [Hsp90] + [Akt] → [Akt_Hsp90];  
 
 Hsp90AktRelease [Akt_Hsp90] → [Akt] + [Hsp90];  
 
 CHIPbinding [CHIP] + [Akt_Hsp90] → [Akt_CHIP_Hsp90];  
 
 CHIPrelease [Akt_CHIP_Hsp90] → [CHIP] + [Akt_Hsp90];  
 
 AktProteasomeBinding [Akt_CHIP_Hsp90] + [Proteasome] → [Akt_Proteasome] + [CHIP] + [Hsp90];  
 
 AktProteasomeRelease [Akt_Proteasome] → [Akt] + [Proteasome];  
 
 AktDegradation [Akt_Proteasome] + [ATP] → [Proteasome] + [ADP];  
 
 Mkp1Synthesis [Source] → [Mkp1];  
 
 Mkp1ProteasomeBinding [Mkp1] + [Proteasome] → [Mkp1_Proteasome];  
 
 Mkp1Degradation [Mkp1_Proteasome] + [ATP] → [Proteasome] + [ADP];  
 
 Mkp1Phosphorylation [Mkp1] + [Hsp70] → [Mkp1_P] + [Hsp70];  
 
 Mkp1Dephosphorylation [Mkp1_P] + [ROS] → [Mkp1] + [ROS];  
 
 p38ROSproduction [p38_P] → [p38_P] + [ROS];  
 
 Hsp70Damage [Hsp70] + [ROS] → [Hsp70_dam] + [ROS];  
 
 Hsp90Damage [Hsp90] + [ROS] → [Hsp90_dam] + [ROS];  
 
 Hsp70DamProteasomeBinding [Hsp70_dam] + [Proteasome] → [Hsp70_Proteasome];  
 
 Hsp90DamProteasomeBinding [Hsp90_dam] + [Proteasome] → [Hsp90_Proteasome];  
 
 Hsp70DamAggregation1 2.0 × [Hsp70_dam] → [AggP];  
 
 Hsp70DamInclusionFormation [Hsp70_dam] + [AggP] → [SeqAggP];  
 
 Hsp90DamAggregation 2.0 × [Hsp90_dam] → [AggP];  
 
 Hsp90DamInclusionFormation [Hsp90_dam] + [AggP] → [SeqAggP];  
 
 Hsp70DamSequestering [Hsp70_dam] + [SeqAggP] → 2.0 × [SeqAggP];  
 
 Hsp90DamSequestering [Hsp90_dam] + [SeqAggP] → 2.0 × [SeqAggP];  
 
 p38CellDeath [p38_P] → [p38_P] + [p38Death] + [CellDeath];  
 
 JnkCellDeath [Jnk_P] → [Jnk_P] + [JNKDeath] + [CellDeath];  
 
 PICellDeath [AggP_Proteasome] → [AggP_Proteasome] + [PIDeath] + [CellDeath];  
 
Rules (3)
 
 Assignment Rule (name: tot_Hsp90) tot_Hsp90 = Hsp90+Hsp90_dam+Hsp90_Proteasome+Hsp90_Hsp90Client+Akt_Hsp90+Akt_CHIP_Hsp90+Hsf1_Hsp90+Hsp90_MisP
 
 Assignment Rule (name: tot_Hsp70) tot_Hsp70 = Hsp70+Hsp70_dam+Hsp70_Proteasome+Hsp70_Hsp70Client+Hsp70_MisP+Hsp70_Ppx
 
 Assignment Rule (name: tot_MisP) tot_MisP = MisP+Hsp70_MisP+Hsp90_MisP
 
Events (1)
 
 DeathOfCell
kalive = 0
 
  Spatial dimensions: 3.0  Compartment size: 1.0
 
 NatP
Compartment: cytosol
Initial amount: 17600.0
 
 MisP
Compartment: cytosol
Initial amount: 0.0
 
 Hsp70
Compartment: cytosol
Initial amount: 1400.0
 
 Hsp90
Compartment: cytosol
Initial amount: 1850.0
 
 Hsp70_dam
Compartment: cytosol
Initial amount: 0.0
 
 Hsp90_dam
Compartment: cytosol
Initial amount: 0.0
 
 Hsp90_Proteasome
Compartment: cytosol
Initial amount: 0.0
 
 Hsp70_Proteasome
Compartment: cytosol
Initial amount: 0.0
 
 Hsp70Client
Compartment: cytosol
Initial amount: 490.0
 
 Hsp90Client
Compartment: cytosol
Initial amount: 590.0
 
 Hsp70_Hsp70Client
Compartment: cytosol
Initial amount: 10.0
 
 Hsp90_Hsp90Client
Compartment: cytosol
Initial amount: 10.0
 
 Akt
Compartment: cytosol
Initial amount: 340.0
 
 Akt_Hsp90
Compartment: cytosol
Initial amount: 30.0
 
 CHIP
Compartment: cytosol
Initial amount: 255.0
 
 Akt_CHIP_Hsp90
Compartment: cytosol
Initial amount: 80.0
 
 Akt_Proteasome
Compartment: cytosol
Initial amount: 0.0
 
 Hsf1
Compartment: cytosol
Initial amount: 5.0
 
 Hsf1_Hsp90
Compartment: cytosol
Initial amount: 95.0
 
 Hsp90_MisP
Compartment: cytosol
Initial amount: 470.0
 
 Hsp70_MisP
Compartment: cytosol
Initial amount: 410.0
 
 Hsf1_Hsf1
Compartment: cytosol
Initial amount: 0.0
 
 Jnk
Compartment: cytosol
Initial amount: 100.0
 
 Jnk_P
Compartment: cytosol
Initial amount: 0.0
 
 Ppx
Compartment: cytosol
Initial amount: 0.0
 
 Mkp1
Compartment: cytosol
Initial amount: 0.0
 
 Mkp1_P
Compartment: cytosol
Initial amount: 100.0
 
 Mkp1_Proteasome
Compartment: cytosol
Initial amount: 0.0
 
 Hsp70_Ppx
Compartment: cytosol
Initial amount: 100.0
 
 Pkc
Compartment: cytosol
Initial amount: 100.0
 
 p38
Compartment: cytosol
Initial amount: 100.0
 
 p38_P
Compartment: cytosol
Initial amount: 0.0
 
 Proteasome
Compartment: cytosol
Initial amount: 500.0
 
 MisP_Proteasome
Compartment: cytosol
Initial amount: 0.0
 
 AggP
Compartment: cytosol
Initial amount: 0.0
 
 SeqAggP
Compartment: cytosol
Initial amount: 0.0
 
 AggP_Proteasome
Compartment: cytosol
Initial amount: 0.0
 
 ROS
Compartment: cytosol
Initial amount: 10.0
 
 ATP
Compartment: cytosol
Initial amount: 10000.0
 
 ADP
Compartment: cytosol
Initial amount: 1000.0
 
 Source
Compartment: cytosol
Initial amount: 1.0
 
 Sink
Compartment: cytosol
Initial amount: 1.0
 
 p38Death
Compartment: cytosol
Initial amount: 0.0
 
 JNKDeath
Compartment: cytosol
Initial amount: 0.0
 
 PIDeath
Compartment: cytosol
Initial amount: 0.0
 
 CellDeath
Compartment: cytosol
Initial amount: 0.0
 
  Spatial dimensions: 3.0  Compartment size: 1.0
 
 Hsf1_Hsf1_Hsf1
Compartment: nucleus
Initial amount: 0.0
 
 Hsf1_Hsf1_Hsf1_P
Compartment: nucleus
Initial amount: 0.0
 
 HSEHsp70
Compartment: nucleus
Initial amount: 2.0
 
 HSEHsp90
Compartment: nucleus
Initial amount: 2.0
 
 HSEHsp70_Hsf1_Hsf1_Hsf1
Compartment: nucleus
Initial amount: 0.0
 
 HSEHsp70_Hsf1_Hsf1_Hsf1_P
Compartment: nucleus
Initial amount: 0.0
 
 HSEHsp90_Hsf1_Hsf1_Hsf1
Compartment: nucleus
Initial amount: 0.0
 
 HSEHsp90_Hsf1_Hsf1_Hsf1_P
Compartment: nucleus
Initial amount: 0.0
 
Global Parameters (65)
 
 ksynNatP
Value: 0.042
Constant
 
 kmisfold
Value: 2.0E-6
Constant
 
 kbinMisPProt
Value: 1.0E-7
Constant
 
 kdegMisP
Value: 0.01
Constant
 
 kagg
Value: 1.0E-8
Constant
 
 kseqagg
Value: 7.0E-7
Constant
 
 kbinAggPProt
Value: 1.0E-5
Constant
 
 kbinHspMisp
Value: 8.0E-6
Constant
 
 krelHspMisp
Value: 8.0E-5
Constant
 
 krefold
Value: 5.5E-4
Constant
 
 kbinHsf1Hsp90
Value: 0.02
 
 krelHsf1Hsp90
Value: 0.5
Constant
 
 kdimerHsf1
Value: 8.0E-5
Constant
 
 ktrimerHsf1
Value: 0.01
Constant
 
 kdetrimerHsf1
Value: 0.5
Constant
 
 kdedimerHsf1
Value: 0.5
Constant
 
 kbinHSEHsf1
Value: 0.05
Constant
 
 krelHSEHsf1
Value: 0.08
Constant
 
 kupregHsp
Value: 0.2
Constant
 
 kbasalsynHsp70
Value: 0.0080
Constant
 
 kbasalsynHsp90
Value: 0.0080
Constant
 
 kbinHsp70Prot
Value: 1.2E-8
Constant
 
 kbinHsp90Prot
Value: 1.0E-8
Constant
 
 kdegHsp70
Value: 0.01
Constant
 
 kdegHsp90
Value: 0.01
Constant
 
 kgenROS
Value: 0.01
 
 kremROS
Value: 0.0010
Constant
 
 kbinHsp70client
Value: 2.0E-4
Constant
 
 krelHsp70client
Value: 5.0
Constant
 
 kbinHsp90client
Value: 2.0E-4
Constant
 
 krelHsp90client
Value: 5.0
 
 kphosJnk
Value: 0.02
Constant
 
 kdephosJnkMkp1
Value: 0.05
Constant
 
 kbinHsp70Ppx
Value: 0.2
Constant
 
 krelHsp70Ppx
Value: 5.0
Constant
 
 kphosHsf1
Value: 0.03
Constant
 
 kdephosHsf1
Value: 0.01
Constant
 
 kbinHSEPhosTriH
Value: 0.1
Constant
 
 krelHSEPhosTriH
Value: 0.08
Constant
 
 kphosp38
Value: 0.02
Constant
 
 kdephosp38Mkp1
Value: 0.05
Constant
 
 kgenROSAggP
Value: 1.0E-6
Constant
 
 ksynAkt
Value: 0.0015
Constant
 
 kbinAktHsp90
Value: 3.7E-4
Constant
 
 krelAktHsp90
Value: 7.0
 
 kbinAktProt
Value: 6.0E-8
Constant
 
 krelAktProt
Value: 1.0E-8
Constant
 
 kdegAkt
Value: 0.01
Constant
 
 kbinCHIP
Value: 2.0E-7
Constant
 
 krelCHIP
Value: 1.0E-8
Constant
 
 ksynMkp1
Value: 1.0E-5
Constant
 
 kbinMkp1Prot
Value: 9.6E-9
Constant
 
 kdegMkp1
Value: 0.01
Constant
 
 kphosMkp1
Value: 0.02
Constant
 
 kdephosMkp1
Value: 0.0010
Constant
 
 kgenROSp38
Value: 1.0E-4
Constant
 
 kdamHsp
Value: 1.0E-8
Constant
 
 kp38death
Value: 1.5E-7
Constant
 
 kJnkdeath
Value: 1.5E-7
Constant
 
 kPIdeath
Value: 2.0E-8
Constant
 
 kp38act
Value: 1.0
 
 kalive
Value: 1.0
 
   tot_Hsp90  
 
   tot_Hsp70  
 
   tot_MisP  
 
Representative curation result(s)
Representative curation result(s) of BIOMD0000000344

Curator's comment: (updated: 21 Jul 2011 17:38:42 BST)

Simulations were performed under three different conditions:
1) normal condition (no stress),
2) moderate stress due to an increase in reactive oxygen species (ROS) i.e. ROS levels were increased by a factor of 4 at time=4hours for a period of 1 hour (not 2 hours as mentioned in the figure 5 legend of the reference publication. This is, a typo in the paper and is clarified by the author) [Refer supporting file: MODEL1005280000_moderatestress.xml] and
3) high stress due to sustained increase in reactive oxygen species (ROS) (here ROS increases with time) [Refer supporting file:MODEL1005280000_highstress.xml].

Supplementary figures S3 (normal condition), S4 (moderate stress condition) and S6 (high stress condition) are reproduced here.

SBML odeSolver was used for model simulation and plots were generated using gnuplot.

Additional file(s)
  • Proctor (2011) - Transcient increase in ROS (moderate stress):
    To obtain this plot, ROS levels should be increased by a factor of 4 at time = 4 hours for a period of 1 hour.
  • Proctor (2011) - Increasing ROS with time (high stress):
    To obtain this plot, constant rate of ROS production should be replaced with a rate that increases linearly with time. This is done by including a time variable in the rate law.
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