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is described by: http://identifiers.org/pubmed/20885783
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reaction: 511652
name: Tang2010_PolyGlutamate
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notes: This a model from the article: Experimental and computational analysis of polyglutamine-mediated cytotoxicity. Tang MY, Proctor CJ, Woulfe J, Gray DA. PLoS Comput Biol. 2010 Sep 23;6(9). 20885783 , Abstract: Expanded polyglutamine (polyQ) proteins are known to be the causative agents of a number of human neurodegenerative diseases but the molecular basis of their cytoxicity is still poorly understood. PolyQ tracts may impede the activity of the proteasome, and evidence from single cell imaging suggests that the sequestration of polyQ into inclusion bodies can reduce the proteasomal burden and promote cell survival, at least in the short term. The presence of misfolded protein also leads to activation of stress kinases such as p38MAPK, which can be cytotoxic. The relationships of these systems are not well understood. We have used fluorescent reporter systems imaged in living cells, and stochastic computer modeling to explore the relationships of polyQ, p38MAPK activation, generation of reactive oxygen species (ROS), proteasome inhibition, and inclusion body formation. In cells expressing a polyQ protein inclusion, body formation was preceded by proteasome inhibition but cytotoxicity was greatly reduced by administration of a p38MAPK inhibitor. Computer simulations suggested that without the generation of ROS, the proteasome inhibition and activation of p38MAPK would have significantly reduced toxicity. Our data suggest a vicious cycle of stress kinase activation and proteasome inhibition that is ultimately lethal to cells. There was close agreement between experimental data and the predictions of a stochastic computer model, supporting a central role for proteasome inhibition and p38MAPK activation in inclusion body formation and ROS-mediated cell death. This model originates from BioModels Database: A Database of Annotated Published Models (http://www.ebi.ac.uk/biomodels/). It is copyright (c) 2005-2010 The BioModels.net Team. For more information see the terms of …
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fast: false
reversible: false

003559
type: SpeciesReference
stoichiometry: 2.0
species: 511561

003547
type: SpeciesReference
stoichiometry: 1.0
species: 511561

003535
type: SpeciesReference
stoichiometry: 1.0
species: 511565

511762
type: Parameter
constant: true
value: 5.0E-7

511741
type: Parameter
constant: true
value: 3.0E-7

511618
type: Reaction
kinetic law: 003475
product: 003463
reactant: 003450
fast: false
reversible: false

003463
type: SpeciesReference
stoichiometry: 1.0
species: 511569

003450
type: SpeciesReference
stoichiometry: 1.0
species: 511568

511589
type: Reaction
fast: false
product: 002263
kinetic law: 002275
reactant: 002214
reactant: 002238
product: 002250
reactant: 002226
reversible: false

002263
type: SpeciesReference
stoichiometry: 1.0
species: 511567

002214
type: SpeciesReference
stoichiometry: 1.0
species: 511544

002238
type: SpeciesReference
stoichiometry: 1.0
species: 511567

002250
type: SpeciesReference
stoichiometry: 1.0
species: 511559

002226
type: SpeciesReference
stoichiometry: 1.0
species: 511558

511639
type: Reaction
kinetic law: 004247
product: 004235
product: 004223
reactant: 004211
fast: false
reversible: false

004235
type: SpeciesReference
stoichiometry: 1.0
species: 511551

004223
type: SpeciesReference
stoichiometry: 1.0
species: 511547

004211
type: SpeciesReference
stoichiometry: 1.0
species: 511552

511642
type: Reaction
kinetic law: 004343
product: 004331
product: 004319
reactant: 004307
fast: false
reversible: false

004331
type: SpeciesReference
stoichiometry: 1.0
species: 511553

004319
type: SpeciesReference
stoichiometry: 1.0
species: 511547

004307
type: SpeciesReference
stoichiometry: 1.0
species: 511554

511656
type: Reaction
kinetic law: 004975
product: 004963
product: 004951
reactant: 004939
fast: false
reversible: false

004963
type: SpeciesReference
stoichiometry: 1.0
species: 511567

004951
type: SpeciesReference
stoichiometry: 1.0
species: 511568

004939
type: SpeciesReference
stoichiometry: 1.0
species: 511568

511763
type: Parameter
constant: true
value: 5.0E-7

511777
type: Parameter
constant: true
value: 2.5E-8

511768
type: Parameter
constant: true
value: 2.0E-6

511591
type: Reaction
reversible: false
reactant: 002299
kinetic law: 002348
product: 002323
reactant: 002311
product: 002335
fast: false
reactant: 002287

002299
type: SpeciesReference
stoichiometry: 1.0
species: 511559

002323
type: SpeciesReference
stoichiometry: 1.0
species: 511560

002311
type: SpeciesReference
stoichiometry: 1.0
species: 511567

002335
type: SpeciesReference
stoichiometry: 1.0
species: 511567

002287
type: SpeciesReference
stoichiometry: 1.0
species: 511544

511734
type: Parameter
constant: true
value: 8.0E-7

511636
type: Reaction
kinetic law: 004114
product: 004102
reactant: 004090
reactant: 004078
fast: false
reversible: false

004102
type: SpeciesReference
stoichiometry: 1.0
species: 511554

004090
type: SpeciesReference
stoichiometry: 1.0
species: 511553

004078
type: SpeciesReference
stoichiometry: 1.0
species: 511547

511615
type: Reaction
kinetic law: 003342
product: 003330
product: 003318
reactant: 003306
fast: false
reversible: false

003330
type: SpeciesReference
stoichiometry: 1.0
species: 511567

003318
type: SpeciesReference
stoichiometry: 1.0
species: 511562

003306
type: SpeciesReference
stoichiometry: 1.0
species: 511562

511603
type: Reaction
kinetic law: 002873
product: 002861
reactant: 002849
reactant: 002837
fast: false
reversible: false

002861
type: SpeciesReference
stoichiometry: 1.0
species: 511562

002849
type: SpeciesReference
stoichiometry: 1.0
species: 511545

002837
type: SpeciesReference
stoichiometry: 1.0
species: 511559

511769
type: Parameter
constant: true
value: 8.0E-5

511581
type: Reaction
kinetic law: 001862
product: 001850
reactant: 001838
fast: false
reversible: false

001850
type: SpeciesReference
stoichiometry: 1.0
species: 511563

001838
type: SpeciesReference
stoichiometry: 1.0
species: 511570

511632
type: Reaction
kinetic law: 003969
product: 003957
reactant: 003945
reactant: 003933
fast: false
reversible: false

003957
type: SpeciesReference
stoichiometry: 1.0
species: 511551

003945
type: SpeciesReference
stoichiometry: 1.0
species: 511550

003933
type: SpeciesReference
stoichiometry: 1.0
species: 511547

511753
type: Parameter
constant: true
value: 0.0017

511592
type: Reaction
kinetic law: 002396
product: 002384
product: 002372
reactant: 002360
fast: false
reversible: false

002384
type: SpeciesReference
stoichiometry: 1.0
species: 511559

002372
type: SpeciesReference
stoichiometry: 1.0
species: 511544

002360
type: SpeciesReference
stoichiometry: 1.0
species: 511560

metaid_0000153
type: Parameter
constant: false
value: NaN
name: oligomers

511609
type: Reaction
kinetic law: 003102
product: 003089
product: 003077
reactant: 003065
fast: false
reversible: false

003089
type: SpeciesReference
stoichiometry: 1.0
species: 511567

003077
type: SpeciesReference
stoichiometry: 1.0
species: 511555

003065
type: SpeciesReference
stoichiometry: 1.0
species: 511555

511637
type: Reaction
kinetic law: 004151
product: 004138
reactant: 004126
fast: false
reversible: false

004138
type: SpeciesReference
stoichiometry: 2.0
species: 511547

004126
type: SpeciesReference
stoichiometry: 1.0
species: 511550

511604
type: Reaction
kinetic law: 002921
product: 002909
reactant: 002897
reactant: 002885
fast: false
reversible: false

002909
type: SpeciesReference
stoichiometry: 1.0
species: 511562

002897
type: SpeciesReference
stoichiometry: 1.0
species: 511545

002885
type: SpeciesReference
stoichiometry: 1.0
species: 511560

511654
type: Reaction
kinetic law: 004879
product: 004867
product: 004854
reactant: 004842
fast: false
reversible: false

004867
type: SpeciesReference
stoichiometry: 1.0
species: 511567

004854
type: SpeciesReference
stoichiometry: 1.0
species: 511553

004842
type: SpeciesReference
stoichiometry: 1.0
species: 511553

511583
type: Reaction
kinetic law: 001911
product: 001899
reactant: 001887
reactant: 001874
fast: false
reversible: false

001899
type: SpeciesReference
stoichiometry: 1.0
species: 511564

001887
type: SpeciesReference
stoichiometry: 1.0
species: 511545

001874
type: SpeciesReference
stoichiometry: 1.0
species: 511563

511775
type: Parameter
constant: false
value: 1.0

511754
type: Parameter
constant: true
value: 2.0E-4

511745
type: Parameter
constant: true
value: 5.0E-7

511577
type: Reaction
kinetic law: 001691
product: 001679
reactant: 001667
fast: false
reversible: false

001679
type: SpeciesReference
stoichiometry: 1.0
species: 511544

001667
type: SpeciesReference
stoichiometry: 1.0
species: 511570

511613
type: Reaction
kinetic law: 003294
product: 003282
product: 003270
reactant: 003258
fast: false
reversible: false

003282
type: SpeciesReference
stoichiometry: 1.0
species: 511567

003270
type: SpeciesReference
stoichiometry: 1.0
species: 511560

003258
type: SpeciesReference
stoichiometry: 1.0
species: 511560

511627
type: Reaction
kinetic law: 003849
product: 003837
product: 003825
reactant: 003813
fast: false
reversible: false

003837
type: SpeciesReference
stoichiometry: 1.0
species: 511545

003825
type: SpeciesReference
stoichiometry: 1.0
species: 511547

003813
type: SpeciesReference
stoichiometry: 1.0
species: 511548

511593
type: Reaction
kinetic law: 002446
product: 002433
product: 002420
reactant: 002408
fast: false
reversible: false

002433
type: SpeciesReference
stoichiometry: 1.0
species: 511558

002420
type: SpeciesReference
stoichiometry: 1.0
species: 511544

002408
type: SpeciesReference
stoichiometry: 1.0
species: 511559

511751
type: Parameter
constant: true
value: 1.0E-9

511731
type: Parameter
constant: true
value: 2.0E-7

511651
type: Reaction
kinetic law: 004734
product: 004721
product: 004709
reactant: 004697
fast: false
reversible: false

004721
type: SpeciesReference
stoichiometry: 1.0
species: 511567

004709
type: SpeciesReference
stoichiometry: 1.0
species: 511550

004697
type: SpeciesReference
stoichiometry: 1.0
species: 511550

511772
type: Parameter
constant: true
value: 0.01

511628
type: Reaction
kinetic law: 003885
product: 003873
reactant: 003861
fast: false
reversible: false

003873
type: SpeciesReference
stoichiometry: 1.0
species: 511545

003861
type: SpeciesReference
stoichiometry: 1.0
species: 511548

W3 CDTF: Wed Dec 22 10:49:21 GMT 2010

511579
type: Reaction
kinetic law: 001789
product: 001777
product: 001765
reactant: 001753
fast: false
reversible: false

001777
type: SpeciesReference
stoichiometry: 1.0
species: 511545

001765
type: SpeciesReference
stoichiometry: 1.0
species: 511544

001753
type: SpeciesReference
stoichiometry: 1.0
species: 511565

511602
type: Reaction
kinetic law: 002824
product: 002812
reactant: 002799
reactant: 002787
fast: false
reversible: false

002812
type: SpeciesReference
stoichiometry: 1.0
species: 511562

002799
type: SpeciesReference
stoichiometry: 1.0
species: 511545

002787
type: SpeciesReference
stoichiometry: 1.0
species: 511558

511645
type: Reaction
kinetic law: 004490
product: 004478
reactant: 004466
reactant: 004454
fast: false
reversible: false

004478
type: SpeciesReference
stoichiometry: 1.0
species: 511562

004466
type: SpeciesReference
stoichiometry: 1.0
species: 511545

004454
type: SpeciesReference
stoichiometry: 1.0
species: 511550

511595
type: Reaction
kinetic law: 002544
product: 002532
product: 002520
reactant: 002507
fast: false
reversible: false

002532
type: SpeciesReference
stoichiometry: 1.0
species: 511555

002520
type: SpeciesReference
stoichiometry: 1.0
species: 511544

002507
type: SpeciesReference
stoichiometry: 1.0
species: 511556

511766
type: Parameter
constant: true
value: 1.0E-10

511757
type: Parameter
constant: true
value: 1.0E-7

511580
type: Reaction
kinetic law: 001825
product: 001813
reactant: 001801
fast: false
reversible: false

001813
type: SpeciesReference
stoichiometry: 1.0
species: 511545

001801
type: SpeciesReference
stoichiometry: 1.0
species: 511565

511611
type: Reaction
kinetic law: 003198
product: 003186
product: 003174
reactant: 003162
fast: false
reversible: false

003186
type: SpeciesReference
stoichiometry: 1.0
species: 511567

003174
type: SpeciesReference
stoichiometry: 1.0
species: 511558

003162
type: SpeciesReference
stoichiometry: 1.0
species: 511558

511737
type: Parameter
constant: true
value: 1.0E-10

W3 CDTF: Mon Sep 27 13:21:56 BST 2010

511625
type: Reaction
kinetic law: 003753
product: 003740
reactant: 003728
fast: false
reversible: false

003740
type: SpeciesReference
stoichiometry: 1.0
species: 511546

003728
type: SpeciesReference
stoichiometry: 1.0
species: 511547

511596
type: Reaction
kinetic law: 002580
product: 002568
reactant: 002556
fast: false
reversible: false

002568
type: SpeciesReference
stoichiometry: 2.0
species: 511544

002556
type: SpeciesReference
stoichiometry: 1.0
species: 511555

511758
type: Parameter
constant: true
value: 5.0E-6

511621
type: Reaction
kinetic law: 003620
product: 003608
reactant: 003595
reactant: 003583
fast: false
reversible: false

003608
type: SpeciesReference
stoichiometry: 2.0
species: 511561

003595
type: SpeciesReference
stoichiometry: 1.0
species: 511561

003583
type: SpeciesReference
stoichiometry: 1.0
species: 511548

511742
type: Parameter
constant: true
value: 2.0E-7

511738
type: Parameter
constant: true
value: 5.0E-7

511600
type: Reaction
kinetic law: 002726
product: 002714
reactant: 002702
reactant: 002690
fast: false
reversible: false

002714
type: SpeciesReference
stoichiometry: 1.0
species: 511562

002702
type: SpeciesReference
stoichiometry: 1.0
species: 511545

002690
type: SpeciesReference
stoichiometry: 1.0
species: 511555

ORG:
  orgname: EMBL-EBI
n:
  given: Vijayalakshmi
  family: Chelliah

ORG:
  orgname: Centre for Integrated Systems Biology of Ageing and Nutrition, Institute for Ageing and Health, Newcastle University, UK
n:
  given: Carole J
  family: Proctor