// Created by libAntimony v2.8.0 model *Passos2010_DNAdamage_CellularSenescence() // Compartments and Species: compartment cell; substanceOnly species Mdm2 in cell, p53 in cell, Mdm2_p53 in cell, Mdm2_mRNA in cell; substanceOnly species p53_mRNA in cell, ATMA in cell, ATMI in cell, p21 in cell; substanceOnly species p21_mRNA in cell, p21step1 in cell, p21step2 in cell; substanceOnly species p53_P in cell, Mdm2_P in cell, p21_basal in cell; substanceOnly species p38 in cell, p38_P in cell, GADD45 in cell, IR in cell; substanceOnly species damDNA in cell, ROS in cell, basalROS in cell, $Sink in cell; substanceOnly species $Source in cell; // Reactions: p53mRNASynthesis: $Source => p53_mRNA; ksynp53mRNA*Source; p53mRNADegradation: p53_mRNA => $Sink; kdegp53mRNA*p53_mRNA; Mdm2Synthesis: Mdm2_mRNA => Mdm2_mRNA + Mdm2; ksynMdm2*Mdm2_mRNA; Mdm2mRNASynthesis1: p53 => p53 + Mdm2_mRNA; ksynMdm2mRNA*p53; Mdm2mRNASynthesis2: p53_P => p53_P + Mdm2_mRNA; ksynMdm2mRNA*p53_P; Mdm2mRNADegradation: Mdm2_mRNA => $Sink; kdegMdm2mRNA*Mdm2_mRNA; Mdm2Degradation: Mdm2 => $Sink; kdegMdm2*Mdm2; p53Synthesis: p53_mRNA => p53 + p53_mRNA; ksynp53*p53_mRNA; p53Degradation: Mdm2_p53 => Mdm2; kdegp53*Mdm2_p53; p53Mdm2IndepDegradation1: p53_P => $Sink; kdegp53mdm2ind*p53_P; p53Mdm2IndepDegradation2: p53 => $Sink; kdegp53mdm2ind*p53; P53_Mdm2Binding: p53 + Mdm2 => Mdm2_p53; kbinMdm2p53*p53*Mdm2; P53_Mdm2Release: Mdm2_p53 => p53 + Mdm2; krelMdm2p53*Mdm2_p53; DNAdamage: IR => IR + damDNA; kdam*IR; DNArepair: damDNA => $Sink; krepair*damDNA; ATMactivation: damDNA + ATMI => damDNA + ATMA; kactATM*damDNA*ATMI; p53phoshorylation: p53 + ATMA => p53_P + ATMA; kphosp53*p53*ATMA; p53dephosorylation: p53_P => p53; kdephosp53*p53_P; Mdm2phoshorylation: Mdm2 + ATMA => Mdm2_P + ATMA; kphosMdm2*Mdm2*ATMA; Mdm2dephosorylation: Mdm2_P => Mdm2; kdephosMdm2*Mdm2_P; Mdm2Pdegradation: Mdm2_P => $Sink; kdegATMMdm2*Mdm2_P; ATMInactivation: ATMA => ATMI; kinactATM*ATMA; p21mRNASynthesis1: p53 => p53 + p21_mRNA; ksynp21mRNAp53*p53; p21mRNASynthesis2: p53_P => p53_P + p21_mRNA; ksynp21mRNAp53P*p53_P; p21mRNADegradation: p21_mRNA => $Sink; kdegp21mRNA*p21_mRNA; p21Synthesis1: p21_mRNA => p21_mRNA + p21step1; ksynp21step1*p21_mRNA; p21Synthesis2: p21step1 => p21step2; ksynp21step2*p21step1; p21Synthesis3: p21step2 => p21; ksynp21step3*p21step2; p21degradation: p21 => $Sink; kdegp21*p21; GADD45activation2: p21 => p21 + GADD45; kGADD45*p21; GADD45degradation: GADD45 => $Sink; kdegGADD45*GADD45; p38activation: p38 + GADD45 => p38_P + GADD45; kphosp38*p38*GADD45; p38inactivation: p38_P => p38; kdephosp38*p38_P; ROSgenerationP38: p38_P => p38_P + ROS; kgenROSp38*p38_P*kp38ROS; ROSremoval: ROS => $Sink; kremROS*ROS; ROSDNAdamage: ROS => ROS + damDNA; kdamROS*ROS; basalROSDNAdamage: basalROS => basalROS + damDNA; kdamBasalROS*basalROS; // Events: stressCell: at time >= 172800: IR = 200; stopStress: at time >= 172860: IR = 0; stopp38ROS: at time >= 691200: kp38ROS = 0.6; // Species initializations: Mdm2 = 5/cell; p53 = 5/cell; Mdm2_p53 = 95/cell; Mdm2_mRNA = 10/cell; p53_mRNA = 10/cell; ATMA = 0; ATMI = 200/cell; p21 = 0; p21_mRNA = 1/cell; p21step1 = 0; p21step2 = 0; p53_P = 0; Mdm2_P = 0; p21_basal = 7/cell; p38 = 100/cell; p38_P = 0; GADD45 = 0; IR = 0; damDNA = 0; ROS = 0; basalROS = 10/cell; Sink = 1/cell; Source = 1/cell; // Compartment initializations: cell = 1; // Variable initializations: kp38ROS = 1; ksynMdm2 = 0.000495; kdegMdm2 = 0.000433; ksynp53 = 0.006; kdegp53 = 0.000825; kdegp53mdm2ind = 8.25e-007; kbinMdm2p53 = 0.001155; krelMdm2p53 = 1.155e-006; ksynMdm2mRNA = 0.0001; kdegMdm2mRNA = 0.0001; kactATM = 2e-005; kdegATMMdm2 = 0.0004; kinactATM = 0.0005; kphosp53 = 0.006; kdephosp53 = 0.5; kphosMdm2 = 2; kdephosMdm2 = 0.5; kphosp38 = 0.008; kdephosp38 = 0.1; kdam = 0.007; krepair = 6e-005; kGADD45 = 4e-006; kdegGADD45 = 1e-005; ksynp53mRNA = 0.001; kdegp53mRNA = 0.0001; ksynp21mRNAp53P = 6e-006; ksynp21mRNAp53 = 6e-008; kdegp21mRNA = 2.4e-005; ksynp21step1 = 0.0004; ksynp21step2 = 4e-005; ksynp21step3 = 4e-005; kdegp21 = 0.00019; kremROS = 0.000383; kgenROSp38 = 0.00045; kdamROS = 1e-005; kdamBasalROS = 1e-009; // Other declarations: var kp38ROS; const cell, ksynMdm2, kdegMdm2, ksynp53, kdegp53, kdegp53mdm2ind, kbinMdm2p53; const krelMdm2p53, ksynMdm2mRNA, kdegMdm2mRNA, kactATM, kdegATMMdm2, kinactATM; const kphosp53, kdephosp53, kphosMdm2, kdephosMdm2, kphosp38, kdephosp38; const kdam, krepair, kGADD45, kdegGADD45, ksynp53mRNA, kdegp53mRNA, ksynp21mRNAp53P; const ksynp21mRNAp53, kdegp21mRNA, ksynp21step1, ksynp21step2, ksynp21step3; const kdegp21, kremROS, kgenROSp38, kdamROS, kdamBasalROS; // Unit definitions: unit substance = item; end