- Author:
- Jeelean <jlim063@aucklanduni.ac.nz>
- Date:
- 2009-07-24 11:27:13+12:00
- Desc:
- Initial commit of proctor_2005
- Permanent Source URI:
- https://models.physiomeproject.org/workspace/proctor_2005/rawfile/000e4aa408a8fbfa229ce89355bdbf8b811c8d8b/proctor_soti_boys_gillespie_shanley_wilkinson_kirkwood_2005.cellml
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<!--
This CellML file was generated on 17/07/2009 at 10:41:19 at a.m. using:
COR (0.9.31.1207)
Copyright 2002-2009 Dr Alan Garny
http://COR.physiol.ox.ac.uk/ - COR@physiol.ox.ac.uk
CellML 1.0 was used to generate this model
http://www.CellML.org/
-->
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<article>
<articleinfo>
<title>Modelling the Actions of Chaperones and Their Role in Ageing</title>
<author>
<firstname>Jeelean</firstname>
<surname>Lim</surname>
<affiliation>
<shortaffil>Bioengineering Institute, University of Auckland</shortaffil>
</affiliation>
</author>
</articleinfo>
<section id="sec_status">
<title>Model Status</title>
<para>
This CellML version of the model has been checked in COR and PCEnv and the model runs to replicate the results as shown in figure 4 of the published paper. The units have been checked and are consistent. This CellML description is deterministic, unlike the stochastic model created and preferred by the authors. A few equations are therefore different from the model in the Biomodels database, such as the rate equations describing the dimerisation of HSF1 and the aggregation of MisP, and the graphs produced have smooth curves since random fluctuations of the intracellular preocesses are not taken into account.
</para>
</section>
<sect1 id="sec_structure">
<title>Model Structure</title>
<para>
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.
</para>
<para>
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. Alzheimers disease, Parkinsons 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.
</para>
<para>
The complete original paper reference is cited below:
</para>
<para>
Modelling the actions of chaperones and their role in ageing, Carole J. Proctor, Csaba Soti, Richard J. Boys, Colin S. Gillespie, Daryl P. Shanley, Darren J. Wilkinson, Thomas B.L. Kirkwood, 2005,
<emphasis>Mech Ageing Dev.</emphasis>
, 126(1), 119-131. <ulink url="http://www.ncbi.nlm.nih.gov/pubmed/15610770">PubMed ID: 15610770</ulink>
</para>
<informalfigure float="0" id="fig_reaction_diagram">
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<title>Figure 1</title>
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<caption>Network diagram of the model: Protein turnover</caption>
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<title>Figure 2</title>
</objectinfo>
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<caption>Network diagram of the model: Autoregulation of Hsp90</caption>
</informalfigure>
</sect1>
</article>
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<ci>v12</ci>
<apply>
<times/>
<ci>k12</ci>
<ci>TriH</ci>
</apply>
</apply>
</math>
</component>
<component name="v13">
<variable name="v13" units="flux" public_interface="out"/>
<variable name="k13" units="first_order_rate_constant" initial_value="0.5"/>
<variable name="DiH" units="molecules" public_interface="in"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>v13</ci>
<apply>
<times/>
<ci>k13</ci>
<ci>DiH</ci>
</apply>
</apply>
</math>
</component>
<component name="v14">
<variable name="v14" units="flux" public_interface="out"/>
<variable name="k14" units="second_order_rate_constant" initial_value="0.05"/>
<variable name="HSE" units="molecules" public_interface="in"/>
<variable name="TriH" units="molecules" public_interface="in"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>v14</ci>
<apply>
<times/>
<ci>k14</ci>
<ci>HSE</ci>
<ci>TriH</ci>
</apply>
</apply>
</math>
</component>
<component name="v15">
<variable name="v15" units="flux" public_interface="out"/>
<variable name="k15" units="first_order_rate_constant" initial_value="0.08"/>
<variable name="HSE_TriH" units="molecules" public_interface="in"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>v15</ci>
<apply>
<times/>
<ci>k15</ci>
<ci>HSE_TriH</ci>
</apply>
</apply>
</math>
</component>
<component name="v16">
<variable name="v16" units="flux" public_interface="out"/>
<variable name="k16" units="first_order_rate_constant" initial_value="1000"/>
<variable name="HSE_TriH" units="molecules" public_interface="in"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>v16</ci>
<apply>
<times/>
<ci>k16</ci>
<ci>HSE_TriH</ci>
</apply>
</apply>
</math>
</component>
<component name="v17">
<variable name="v17" units="flux" public_interface="out"/>
<variable name="k17" units="second_order_rate_constant" initial_value="8.02e-9"/>
<variable name="Hsp90" units="molecules" public_interface="in"/>
<variable name="ATP" units="molecules" public_interface="in"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>v17</ci>
<apply>
<times/>
<ci>k17</ci>
<ci>Hsp90</ci>
<ci>ATP</ci>
</apply>
</apply>
</math>
</component>
<component name="v18">
<variable name="v18" units="flux" public_interface="out"/>
<variable name="k18" units="first_order_rate_constant" initial_value="12"/>
<variable name="ADP" units="molecules" public_interface="in"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>v18</ci>
<apply>
<times/>
<ci>k18</ci>
<ci>ADP</ci>
</apply>
</apply>
</math>
</component>
<component name="v19">
<variable name="v19" units="flux" public_interface="out"/>
<variable name="k19" units="first_order_rate_constant" initial_value="0.02"/>
<variable name="ATP" units="molecules" public_interface="in"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>v19</ci>
<apply>
<times/>
<ci>k19</ci>
<ci>ATP</ci>
</apply>
</apply>
</math>
</component>
<component name="v20">
<variable name="v20" units="flux" public_interface="out"/>
<variable name="k20" units="flux" initial_value="0.1"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>v20</ci>
<ci>k20</ci>
</apply>
</math>
</component>
<component name="v21">
<variable name="v21" units="flux" public_interface="out"/>
<variable name="k21" units="first_order_rate_constant" initial_value="0.00001"/>
<variable name="ROS" units="molecules" public_interface="in"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>v21</ci>
<apply>
<times/>
<ci>k21</ci>
<ci>ROS</ci>
</apply>
</apply>
</math>
</component>
<connection>
<map_components component_1="NatP" component_2="environment"/>
<map_variables variable_1="time" variable_2="time"/>
</connection>
<connection>
<map_components component_1="MisP" component_2="environment"/>
<map_variables variable_1="time" variable_2="time"/>
</connection>
<connection>
<map_components component_1="MCom" component_2="environment"/>
<map_variables variable_1="time" variable_2="time"/>
</connection>
<connection>
<map_components component_1="Hsp90" component_2="environment"/>
<map_variables variable_1="time" variable_2="time"/>
</connection>
<connection>
<map_components component_1="HCom" component_2="environment"/>
<map_variables variable_1="time" variable_2="time"/>
</connection>
<connection>
<map_components component_1="HSF1" component_2="environment"/>
<map_variables variable_1="time" variable_2="time"/>
</connection>
<connection>
<map_components component_1="DiH" component_2="environment"/>
<map_variables variable_1="time" variable_2="time"/>
</connection>
<connection>
<map_components component_1="TriH" component_2="environment"/>
<map_variables variable_1="time" variable_2="time"/>
</connection>
<connection>
<map_components component_1="HSE_TriH" component_2="environment"/>
<map_variables variable_1="time" variable_2="time"/>
</connection>
<connection>
<map_components component_1="HSE" component_2="environment"/>
<map_variables variable_1="time" variable_2="time"/>
</connection>
<connection>
<map_components component_1="AggP" component_2="environment"/>
<map_variables variable_1="time" variable_2="time"/>
</connection>
<connection>
<map_components component_1="ROS" component_2="environment"/>
<map_variables variable_1="time" variable_2="time"/>
</connection>
<connection>
<map_components component_1="ATP" component_2="environment"/>
<map_variables variable_1="time" variable_2="time"/>
</connection>
<connection>
<map_components component_1="ADP" component_2="environment"/>
<map_variables variable_1="time" variable_2="time"/>
</connection>
<connection>
<map_components component_1="NatP" component_2="v1"/>
<map_variables variable_1="v1" variable_2="v1"/>
</connection>
<connection>
<map_components component_1="NatP" component_2="v2"/>
<map_variables variable_1="v2" variable_2="v2"/>
<map_variables variable_1="NatP" variable_2="NatP"/>
</connection>
<connection>
<map_components component_1="NatP" component_2="v5"/>
<map_variables variable_1="v5" variable_2="v5"/>
</connection>
<connection>
<map_components component_1="MisP" component_2="v2"/>
<map_variables variable_1="v2" variable_2="v2"/>
</connection>
<connection>
<map_components component_1="MisP" component_2="v3"/>
<map_variables variable_1="v3" variable_2="v3"/>
<map_variables variable_1="MisP" variable_2="MisP"/>
</connection>
<connection>
<map_components component_1="MisP" component_2="v4"/>
<map_variables variable_1="v4" variable_2="v4"/>
</connection>
<connection>
<map_components component_1="MisP" component_2="v6"/>
<map_variables variable_1="v6" variable_2="v6"/>
<map_variables variable_1="MisP" variable_2="MisP"/>
</connection>
<connection>
<map_components component_1="MisP" component_2="v7"/>
<map_variables variable_1="v7" variable_2="v7"/>
<map_variables variable_1="MisP" variable_2="MisP"/>
</connection>
<connection>
<map_components component_1="MCom" component_2="v3"/>
<map_variables variable_1="v3" variable_2="v3"/>
</connection>
<connection>
<map_components component_1="MCom" component_2="v4"/>
<map_variables variable_1="v4" variable_2="v4"/>
<map_variables variable_1="MCom" variable_2="MCom"/>
</connection>
<connection>
<map_components component_1="MCom" component_2="v5"/>
<map_variables variable_1="v5" variable_2="v5"/>
<map_variables variable_1="MCom" variable_2="MCom"/>
</connection>
<connection>
<map_components component_1="Hsp90" component_2="v5"/>
<map_variables variable_1="v5" variable_2="v5"/>
</connection>
<connection>
<map_components component_1="Hsp90" component_2="v4"/>
<map_variables variable_1="v4" variable_2="v4"/>
</connection>
<connection>
<map_components component_1="Hsp90" component_2="v9"/>
<map_variables variable_1="v9" variable_2="v9"/>
</connection>
<connection>
<map_components component_1="Hsp90" component_2="v16"/>
<map_variables variable_1="v16" variable_2="v16"/>
</connection>
<connection>
<map_components component_1="Hsp90" component_2="v3"/>
<map_variables variable_1="v3" variable_2="v3"/>
<map_variables variable_1="Hsp90" variable_2="Hsp90"/>
</connection>
<connection>
<map_components component_1="Hsp90" component_2="v8"/>
<map_variables variable_1="v8" variable_2="v8"/>
<map_variables variable_1="Hsp90" variable_2="Hsp90"/>
</connection>
<connection>
<map_components component_1="Hsp90" component_2="v17"/>
<map_variables variable_1="v17" variable_2="v17"/>
<map_variables variable_1="Hsp90" variable_2="Hsp90"/>
</connection>
<connection>
<map_components component_1="HCom" component_2="v8"/>
<map_variables variable_1="v8" variable_2="v8"/>
</connection>
<connection>
<map_components component_1="HCom" component_2="v9"/>
<map_variables variable_1="v9" variable_2="v9"/>
<map_variables variable_1="HCom" variable_2="HCom"/>
</connection>
<connection>
<map_components component_1="HSF1" component_2="v13"/>
<map_variables variable_1="v13" variable_2="v13"/>
</connection>
<connection>
<map_components component_1="HSF1" component_2="v12"/>
<map_variables variable_1="v12" variable_2="v12"/>
</connection>
<connection>
<map_components component_1="HSF1" component_2="v8"/>
<map_variables variable_1="v8" variable_2="v8"/>
<map_variables variable_1="HSF1" variable_2="HSF1"/>
</connection>
<connection>
<map_components component_1="HSF1" component_2="v9"/>
<map_variables variable_1="v9" variable_2="v9"/>
</connection>
<connection>
<map_components component_1="HSF1" component_2="v10"/>
<map_variables variable_1="v10" variable_2="v10"/>
<map_variables variable_1="HSF1" variable_2="HSF1"/>
</connection>
<connection>
<map_components component_1="DiH" component_2="v10"/>
<map_variables variable_1="v10" variable_2="v10"/>
</connection>
<connection>
<map_components component_1="DiH" component_2="v11"/>
<map_variables variable_1="v11" variable_2="v11"/>
<map_variables variable_1="DiH" variable_2="DiH"/>
</connection>
<connection>
<map_components component_1="DiH" component_2="v12"/>
<map_variables variable_1="v12" variable_2="v12"/>
</connection>
<connection>
<map_components component_1="DiH" component_2="v13"/>
<map_variables variable_1="v13" variable_2="v13"/>
<map_variables variable_1="DiH" variable_2="DiH"/>
</connection>
<connection>
<map_components component_1="TriH" component_2="v11"/>
<map_variables variable_1="v11" variable_2="v11"/>
</connection>
<connection>
<map_components component_1="TriH" component_2="v12"/>
<map_variables variable_1="v12" variable_2="v12"/>
<map_variables variable_1="TriH" variable_2="TriH"/>
</connection>
<connection>
<map_components component_1="TriH" component_2="v14"/>
<map_variables variable_1="v14" variable_2="v14"/>
<map_variables variable_1="TriH" variable_2="TriH"/>
</connection>
<connection>
<map_components component_1="TriH" component_2="v15"/>
<map_variables variable_1="v15" variable_2="v15"/>
</connection>
<connection>
<map_components component_1="HSE_TriH" component_2="v14"/>
<map_variables variable_1="v14" variable_2="v14"/>
</connection>
<connection>
<map_components component_1="HSE_TriH" component_2="v15"/>
<map_variables variable_1="v15" variable_2="v15"/>
<map_variables variable_1="HSE_TriH" variable_2="HSE_TriH"/>
</connection>
<connection>
<map_components component_1="HSE_TriH" component_2="v16"/>
<map_variables variable_1="v16" variable_2="v16"/>
<map_variables variable_1="HSE_TriH" variable_2="HSE_TriH"/>
</connection>
<connection>
<map_components component_1="HSE" component_2="v14"/>
<map_variables variable_1="v14" variable_2="v14"/>
<map_variables variable_1="HSE" variable_2="HSE"/>
</connection>
<connection>
<map_components component_1="HSE" component_2="v15"/>
<map_variables variable_1="v15" variable_2="v15"/>
</connection>
<connection>
<map_components component_1="AggP" component_2="v7"/>
<map_variables variable_1="v7" variable_2="v7"/>
</connection>
<connection>
<map_components component_1="AggP" component_2="v7b"/>
<map_variables variable_1="v7b" variable_2="v7b"/>
<map_variables variable_1="AggP" variable_2="AggP"/>
</connection>
<connection>
<map_components component_1="ROS" component_2="v2"/>
<map_variables variable_1="v2" variable_2="v2"/>
<map_variables variable_1="ROS" variable_2="ROS"/>
</connection>
<connection>
<map_components component_1="ROS" component_2="v20"/>
<map_variables variable_1="v20" variable_2="v20"/>
</connection>
<connection>
<map_components component_1="ROS" component_2="v21"/>
<map_variables variable_1="v21" variable_2="v21"/>
<map_variables variable_1="ROS" variable_2="ROS"/>
</connection>
<connection>
<map_components component_1="ATP" component_2="v5"/>
<map_variables variable_1="v5" variable_2="v5"/>
<map_variables variable_1="ATP" variable_2="ATP"/>
</connection>
<connection>
<map_components component_1="ATP" component_2="v6"/>
<map_variables variable_1="v6" variable_2="v6"/>
<map_variables variable_1="ATP" variable_2="ATP"/>
</connection>
<connection>
<map_components component_1="ATP" component_2="v17"/>
<map_variables variable_1="v17" variable_2="v17"/>
<map_variables variable_1="ATP" variable_2="ATP"/>
</connection>
<connection>
<map_components component_1="ATP" component_2="v18"/>
<map_variables variable_1="v18" variable_2="v18"/>
</connection>
<connection>
<map_components component_1="ATP" component_2="v19"/>
<map_variables variable_1="v19" variable_2="v19"/>
<map_variables variable_1="ATP" variable_2="ATP"/>
</connection>
<connection>
<map_components component_1="ADP" component_2="v5"/>
<map_variables variable_1="v5" variable_2="v5"/>
</connection>
<connection>
<map_components component_1="ADP" component_2="v6"/>
<map_variables variable_1="v6" variable_2="v6"/>
</connection>
<connection>
<map_components component_1="ADP" component_2="v17"/>
<map_variables variable_1="v17" variable_2="v17"/>
</connection>
<connection>
<map_components component_1="ADP" component_2="v18"/>
<map_variables variable_1="v18" variable_2="v18"/>
<map_variables variable_1="ADP" variable_2="ADP"/>
</connection>
<connection>
<map_components component_1="ADP" component_2="v19"/>
<map_variables variable_1="v19" variable_2="v19"/>
</connection>
<connection>
<map_components component_1="v7b" component_2="MisP"/>
<map_variables variable_1="MisP" variable_2="MisP"/>
</connection>
<connection>
<map_components component_1="v11" component_2="HSF1"/>
<map_variables variable_1="HSF1" variable_2="HSF1"/>
<map_variables variable_1="v11" variable_2="v11"/>
</connection>
</model>
