Analysis of a mathematical model of apoptosis: individual differences and malfunction in programmed cell death

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dc.authorid0000-0001-5920-0400
dc.authorscopusid8754351000
dc.authorscopusid54279389500
dc.authorscopusid6604017391
dc.authorwosidBağcı, Elife Zerrin/A-9660-2016
dc.contributor.authorBağcı, Elife Zerrin
dc.contributor.authorSen, S. Murat
dc.contributor.authorÇamurdan, Mehmet C.
dc.date.accessioned2022-05-11T14:28:29Z
dc.date.available2022-05-11T14:28:29Z
dc.date.issued2013
dc.departmentFakülteler, Fen Edebiyat Fakültesi, Biyoloji Bölümü
dc.descriptionSCAI 10th International Conference on Complexity in Acute Illness (ICCAI) -- SEP, 2011 -- Bonn, GERMANY
dc.description.abstractApoptosis is an important area of research because of its role in keeping a mature multicellular organism's number of cells constant, hence, ensuring that the organism does not have cell accumulation that may transform into cancer with additional hallmarks. Firstly, we have carried out sensitivity analysis on an existing mathematical mitochondria-dependent apoptosis model to find out which parameters have a role in causing monostable cell survival, which may, in turn, lead to malfunction in apoptosis. We have then generated three base parameter sets that represent healthy cells. These parameter sets were built by changing the sensitive parameters while preserving the bistability. For each base set, we varied the proapoptotic and antiapoptotic production rates, to yield new sets for the cells that have malfunctioning apoptosis. In a hypothetical cell model, we simulated caspase-3 activation by numerically integrating the governing ordinary differential equations of a mitochondria-dependent apoptosis model. These simulations were carried out for four potential treatments, namely: (1) proteasome inhibitor treatment, (2) Bcl-2 inhibitor treatment, (3) IAP inhibitor treatment, (4) Bid-like synthetic peptides treatment. The results suggest that the proteasome inhibitor treatment is the most effective treatment, though it may have severe side effects. For this treatment, the amount of proteasome inhibitor needed for caspase-3 activation may be different for hypothetical cells with a different pro- or anti-apoptotic protein defect. It is also found that caspase-3 can be activated by Bcl-2 inhibitor treatment only in those hypothetical malfunctioning cells with Bax deficiency but not in others. These results are in line with the view that molecular heterogeneity in individuals may be an important factor in determining the individuals' positive or negative responses to treatments.
dc.description.sponsorshipSoc Complex Acute Illness (SCAI)
dc.identifier.doi10.1007/s10877-013-9468-z
dc.identifier.endpage479
dc.identifier.issn1387-1307
dc.identifier.issn1573-2614
dc.identifier.issue4en_US
dc.identifier.pmid23604638
dc.identifier.scopus2-s2.0-84879552009
dc.identifier.scopusqualityQ2
dc.identifier.startpage465
dc.identifier.urihttps://doi.org/10.1007/s10877-013-9468-z
dc.identifier.urihttps://hdl.handle.net/20.500.11776/6843
dc.identifier.volume27
dc.identifier.wosWOS:000321261400012
dc.identifier.wosqualityQ3
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakScopus
dc.indekslendigikaynakPubMed
dc.institutionauthorBağcı, Elife Zerrin
dc.language.isoen
dc.publisherSpringer Heidelberg
dc.relation.ispartofJournal of Clinical Monitoring and Computing
dc.relation.publicationcategoryKonferans Öğesi - Uluslararası - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/openAccess
dc.subjectSimulations of apoptosis malfunction
dc.subjectVariability in individuals
dc.subjectTreatments of malfunction in apoptosis
dc.subjectCaspase Activation
dc.subjectPathway
dc.subjectCancer
dc.subjectMitochondrial
dc.subjectBistability
dc.subjectMechanisms
dc.subjectSimulation
dc.subjectResistance
dc.subjectDynamics
dc.subjectSurvival
dc.titleAnalysis of a mathematical model of apoptosis: individual differences and malfunction in programmed cell death
dc.typeConference Object

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