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BIOMD0000000091 - Proctor2005 - Actions of chaperones and their role in ageing

 

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Reference Publication
Publication ID: 15610770
Proctor CJ, Soti C, Boys RJ, Gillespie CS, Shanley DP, Wilkinson DJ, Kirkwood TB.
Modelling the actions of chaperones and their role in ageing.
Mech. Ageing Dev. 2005 Jan; 126(1): 119-131
Henry Wellcome Laboratory for Biogerontology Research, School of Clinical and Medical Sciences-Gerontology, University of Newcastle, Newcastle upon Tyne NE4 6BE, UK. c.j.proctor@ncl.ac.uk  [more]
Model
Original Model: BIOMD0000000091.xml.origin
Submitter: Carole Proctor
Submission ID: MODEL2223638385
Submission Date: 08 Mar 2007 19:29:11 UTC
Last Modification Date: 03 Jun 2014 20:38:41 UTC
Creation Date: 26 Feb 2007 13:30:45 UTC
Encoders:  Carole Proctor
   Enuo He
set #1
bqbiol:hasTaxon Taxonomy cellular organisms
bqbiol:isVersionOf Gene Ontology response to heat
Gene Ontology cell aging
Gene Ontology chaperone mediated protein folding requiring cofactor
set #2
bqbiol:hasVersion Human Disease Ontology DOID:14330
Human Disease Ontology DOID:10652
Human Disease Ontology cataract
Notes
Proctor2005 - Actions of chaperones and their role in ageing

This model is described in the article:

Proctor CJ, Soti C, Boys RJ, Gillespie CS, Shanley DP, Wilkinson DJ, Kirkwood TB.
Mech. Ageing Dev. 2005 Jan; 126(1): 119-131

Abstract:

Many molecular chaperones are also known as heat shock proteins because they are synthesised in increased amounts after brief exposure of cells to elevated temperatures. They have many cellular functions and are involved in the folding of nascent proteins, the re-folding of denatured proteins, the prevention of protein aggregation, and assisting the targeting of proteins for degradation by the proteasome and lysosomes. They also have a role in apoptosis and are involved in modulating signals for immune and inflammatory responses. Stress-induced transcription of heat shock proteins requires the activation of heat shock factor (HSF). Under normal conditions, HSF is bound to heat shock proteins resulting in feedback repression. During stress, cellular proteins undergo denaturation and sequester heat shock proteins bound to HSF, which is then able to become transcriptionally active. The induction of heat shock proteins is impaired with age and there is also a decline in chaperone function. Aberrant/damaged proteins accumulate with age and are implicated in several important age-related conditions (e.g. Alzheimer's disease, Parkinson's disease, and cataract). Therefore, the balance between damaged proteins and available free chaperones may be greatly disturbed during ageing. We have developed a mathematical model to describe the heat shock system. The aim of the model is two-fold: to explore the heat shock system and its implications in ageing; and to demonstrate how to build a model of a biological system using our simulation system (biology of ageing e-science integration and simulation (BASIS)).

To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication for more information.

Model
Publication ID: 15610770 Submission Date: 08 Mar 2007 19:29:11 UTC Last Modification Date: 03 Jun 2014 20:38:41 UTC Creation Date: 26 Feb 2007 13:30:45 UTC
Mathematical expressions
Reactions
proteinSynthesis misfolding Hsp90MisPBinding unsuccessfulRefolding
refolding proteinDegradation proteinAggregation1 proteinAggregation2
Hsp90HSF1Binding Hsp90HSF1Release dimerisation trimerisation
deTrimerisation deDimerisation HSETriHBinding HSETriHRelease
Hsp90Transcription Hsp90Degradation countTime ATPformation
ATPconsumption radicalFormation radicalScavenging  
Physical entities
Compartments Species
compartment Hsp90 HCom HSF1
MisP MCom TriH
DiH NatP AggP
HSE HSETriH X
ROS ATP ADP
source    
Global parameters
k1 k2 k3 k4
k5 k6 k7 k8
k9 k10 k11 k12
k13 k14 k15 k16
k17 k18 k19 k20
k21      
Reactions (23)
 
 proteinSynthesis 0.0 × [source] → [NatP];  
 
 misfolding [NatP] + [ROS] → [MisP] + [ROS];  
 
 Hsp90MisPBinding [MisP] + [Hsp90] → [MCom];  
 
 unsuccessfulRefolding [MCom] → [MisP] + [Hsp90];  
 
 refolding [MCom] + [ATP] → [Hsp90] + [NatP] + [ADP];  
 
 proteinDegradation [MisP] + [ATP] → [ADP];  
 
 proteinAggregation1 2.0 × [MisP] → [AggP];  
 
 proteinAggregation2 [MisP] + [AggP] → 2.0 × [AggP];  
 
 Hsp90HSF1Binding [Hsp90] + [HSF1] → [HCom];  
 
 Hsp90HSF1Release [HCom] → [Hsp90] + [HSF1];  
 
 dimerisation 2.0 × [HSF1] → [DiH];  
 
 trimerisation [HSF1] + [DiH] → [TriH];  
 
 deTrimerisation [TriH] → [HSF1] + [DiH];  
 
 deDimerisation [DiH] → 2.0 × [HSF1];  
 
 HSETriHBinding [TriH] + [HSE] → [HSETriH];  
 
 HSETriHRelease [HSETriH] → [HSE] + [TriH];  
 
 Hsp90Transcription [HSETriH] → [HSETriH] + [Hsp90];  
 
 Hsp90Degradation [Hsp90] + [ATP] → [ADP];  
 
 countTime 0.0 × [source] → [X];  
 
 ATPformation [ADP] → [ATP];  
 
 ATPconsumption [ATP] → [ADP];  
 
 radicalFormation 0.0 × [source] → [ROS];  
 
 radicalScavenging [ROS] → ;  
 
  Spatial dimensions: 3.0  Compartment size: 1.0
 
 Hsp90
Compartment: compartment
Initial amount: 300000.0
 
 HCom
Compartment: compartment
Initial amount: 5900.0
 
 HSF1
Compartment: compartment
Initial amount: 100.0
 
   MisP
Compartment: compartment
Initial amount: 0.0
 
 MCom
Compartment: compartment
Initial amount: 0.0
 
 TriH
Compartment: compartment
Initial amount: 0.0
 
 DiH
Compartment: compartment
Initial amount: 0.0
 
   NatP
Compartment: compartment
Initial amount: 6000000.0
 
   AggP
Compartment: compartment
Initial amount: 0.0
 
   HSE
Compartment: compartment
Initial amount: 1.0
 
   HSETriH
Compartment: compartment
Initial amount: 0.0
 
   X
Compartment: compartment
Initial amount: 0.0
 
 ROS
Compartment: compartment
Initial amount: 100.0
 
 ATP
Compartment: compartment
Initial amount: 10000.0
 
 ADP
Compartment: compartment
Initial amount: 1000.0
 
   source
Compartment: compartment
Initial amount: 0.0
 
Global Parameters (21)
 
   k1
Value: 10.0
Constant
 
   k2
Value: 2.0E-5
Constant
 
   k3
Value: 50.0
Constant
 
   k4
Value: 1.0E-5
Constant
 
   k5
Value: 4.0E-6
Constant
 
   k6
Value: 6.0E-7
Constant
 
   k7
Value: 1.0E-7
Constant
 
   k8
Value: 500.0
Constant
 
   k9
Value: 1.0
Constant
 
   k10
Value: 0.01
Constant
 
   k11
Value: 100.0
Constant
 
   k12
Value: 0.5
Constant
 
   k13
Value: 0.5
Constant
 
   k14
Value: 0.05
Constant
 
   k15
Value: 0.08
Constant
 
   k16
Value: 1000.0
Constant
 
   k17
Value: 8.02E-9
Constant
 
   k18
Value: 12.0
Constant
 
   k19
Value: 0.02
Constant
 
   k20
Value: 0.1
Constant
 
   k21
Value: 0.0010
Constant
 
Representative curation result(s)
Representative curation result(s) of BIOMD0000000091

Curator's comment: (updated: 28 Feb 2007 15:55:51 GMT)

Figure2A has been reproduced by Gillespie2.

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