Yeast Apoptosis
Ontology highlight
ABSTRACT:
SUBMITTER: Tomas Helikar
PROVIDER: 2135 | Cell Collective |
REPOSITORIES: Cell Collective
Publications
Boolean model of yeast apoptosis as a tool to study yeast and human apoptotic regulations.
Kazemzadeh Laleh L Cvijovic Marija M Petranovic Dina D
Frontiers in physiology 20121210
Programmed cell death (PCD) is an essential cellular mechanism that is evolutionary conserved, mediated through various pathways and acts by integrating different stimuli. Many diseases such as neurodegenerative diseases and cancers are found to be caused by, or associated with, regulations in the cell death pathways. Yeast Saccharomyces cerevisiae, is a unicellular eukaryotic organism that shares with human cells components and pathways of the PCD and is therefore used as a model organism. Bool ...[more]
Similar Datasets
Project description:This model is from the article:
Heterogeneity Reduces Sensitivity of Cell Death for TNF-Stimuli
Schliemann M, Bullinger E, Borchers S, Allgower F, Findeisen R, Scheurich P. BMC Syst Biol.
2011 Dec 28;5(1):204. 22204418
,
Abstract:
BACKGROUND:
Apoptosis is a form of programmed cell death essential for the maintenance of homeostasis and the removal of potentially damaged cells in multicellular organisms. By binding its cognate membrane receptor, TNF receptor type 1 (TNF-R1), the proinflammatory cytokine Tumor Necrosis Factor (TNF) activates pro-apoptotic signaling via caspase activation, but at the same time also stimulates nuclear factor kappaB (NF-kappaB)-mediated survival pathways. Differential dose-response relationships of these two major TNF signaling pathways have been described experimentally and using mathematical modeling. However, the quantitative analysis of the complex interplay between pro- and anti-apoptotic signaling pathways is an open question as it is challenging for several reasons: the overall signaling network is complex, various time scales are present, and cells respond quantitatively and qualitatively in a heterogeneous manner.
RESULTS:
This study analyzes the complex interplay of the crosstalk of TNF-R1 induced pro- and anti-apoptotic signaling pathways based on an experimentally validated mathematical model. The mathematical model describes the temporal responses on both the single cell level as well as the level of a heterogeneous cell population, as observed in the respective quantitative experiments using TNF-R1 stimuli of different strengths and durations. Global sensitivity of the heterogeneous population was quantified by measuring the average gradient of time of death versus each population parameter. This global sensitivity analysis uncovers the concentrations of Caspase-8 and Caspase-3, and their respective inhibitors BAR and XIAP, as key elements for deciding the cell's fate. A simulated knockout of the NF-kappaB-mediated anti-apoptotic signaling reveals the importance of this pathway for delaying the time of death, reducing the death rate in the case of pulse stimulation and significantly increasing cell-to-cell variability.
CONCLUSIONS:
Cell ensemble modeling of a heterogeneous cell population including a global sensitivity analysis presented here allowed us to illuminate the role of the different elements and parameters on apoptotic signaling. The receptors serve to transmit the external stimulus; procaspases and their inhibitors control the switching from life to death, while NF-kappaB enhances the heterogeneity of the cell population. The global sensitivity analysis of the cell population model further revealed an unexpected impact of heterogeneity, i.e. the reduction of parametric sensitivity.
Note:
SBML model generated from Matlab system description
on 12-July-2011 21:08:15 by
exportSBML Copyright Eric Bullinger 2007-2011
2024-09-02 | BIOMD0000000407 | BioModels
Project description:The hepatitis E virus (HEV), a non enveloped RNA virus, causes viral hepatitis. The viral open reading frame 2 (ORF2) protein represents the capsid protein of HEV which is known to cause endoplasmic reticulum stress in ORF2 expressing cells. The initiation of endoplasmic reticulum stress induced apoptosis mainly involves the transcriptional activation of pro-apoptotic gene CHOP which will further trigger the major apoptotic pathways. However, the activation of CHOP by ORF2 protein in this study does not induce apoptotic markers such as Bax translocation to mitochondria. We have used the Affymetrix microarray platform to screen the pro-apoptotic effects induced by the expression of ORF2 protein in human hepatic cell lines (Huh7). The Huh7 cells were transduced either with recombinant adenovirus encoding the HEV ORF2 (Ad-ORF2) or an adenovirus encoding the green fluorescent protein (Ad-GFP). The array results consistently showed an ORF2 specific induction of mRNA corresponding to the chaperones Hsp72, Hsp70B’ and co-chaperone Hsp40. These studies provide further mechanisms of the ER stress mediated pro apoptotic effects caused by the ORF2 protein and its potential role for the activation of anti-apoptotic activity of the host cell. We used microarray to screen the host genes were regulated by the expression of the hepatitis E virus capsid protein. Huh7 cells transduced with Ad-GFP (control) or with Ad-HEV ORF2.
2012-12-01 | E-GEOD-29061 | biostudies-arrayexpress
Project description:Disruption of circadian clocks exacerbates various diseases, in part likely due to impaired stress resistance. It is unclear how nearly lethal stresses affect circadian clocks. We found that near-lethal doses of reactive oxygen species (ROS)-induced critical oxidative stress (cOS) at the branch point of life and death resets circadian clocks, synergistically evoking protective responses for cell survival. The cOS-triggered clock resetting and pro-survival responses are mediated by transcription factor, central clock-regulatory BMAL1 and heat shock stress-responsive (HSR) HSF1. Casein kinase II (CK2) M-bM-^@M-^Smediated phosphorylation regulates dimerization and function of BMAL1 and HSF1 to control the cOS-evoked responses. The core cOS-responsive transcriptome includes CK2-orchestrated crosstalk between the circadian, HSR, NFM-NM-:B-mediated anti-apoptotic, and Nrf2-mediated anti-oxidant pathways. This novel circadian-adaptive signaling system likely plays fundamental protective roles in ROS-inducible disorders, various diseases, and death. Gene expression was measured 4h, 20h and 32h after treatment with 5 mM H2O2 for 10 min.
2013-11-09 | E-GEOD-47955 | biostudies-arrayexpress
Project description:Human induced neurons and primary murine glia were subjected to a controlled in vitro model of mechanical compression to determine how solid stress—similar to forces present in glioblastoma—directly alters neuronal and glial transcriptional programs. RNA sequencing was performed after 24 hours of compression, with species-specific alignment enabling independent analysis of neuronal and glial responses. Compressed human neurons showed strong activation of hypoxia-responsive metabolic genes, pro-inflammatory signaling pathways, and intrinsic apoptotic programs. Murine glia exhibited parallel induction of hypoxia and apoptotic pathways, accompanied by robust NF-κB/AP-1-driven inflammatory cytokine expression characteristic of astrocytic and microglial activation. These data define the conserved transcriptional responses by which neurons and glia detect and respond to solid stress, providing a resource for understanding mechanotransduction and neuroinflammatory signaling in diseases characterized by mass effect, including glioblastoma.
2025-12-18 | GSE313799 | GEO
Project description:This a model from the article:
Computational insights on the competing effects of nitric oxide in regulating
apoptosis.
Bagci EZ, Vodovotz Y, Billiar TR, Ermentrout B, Bahar I. PLoS One
2008 May 28;3(5):e2249 18509469
,
Abstract:
Despite the establishment of the important role of nitric oxide (NO) on
apoptosis, a molecular-level understanding of the origin of its dichotomous pro-
and anti-apoptotic effects has been elusive. We propose a new mathematical model
for simulating the effects of nitric oxide (NO) on apoptosis. The new model
integrates mitochondria-dependent apoptotic pathways with NO-related reactions,
to gain insights into the regulatory effect of the reactive NO species N(2)O(3),
non-heme iron nitrosyl species (FeL(n)NO), and peroxynitrite (ONOO(-)). The
biochemical pathways of apoptosis coupled with NO-related reactions are
described by ordinary differential equations using mass-action kinetics. In the
absence of NO, the model predicts either cell survival or apoptosis (a bistable
behavior) with shifts in the onset time of apoptotic response depending on the
strength of extracellular stimuli. Computations demonstrate that the relative
concentrations of anti- and pro-apoptotic reactive NO species, and their
interplay with glutathione, determine the net anti- or pro-apoptotic effects at
long time points. Interestingly, transient effects on apoptosis are also
observed in these simulations, the duration of which may reach up to hours,
despite the eventual convergence to an anti-apoptotic state. Our computations
point to the importance of precise timing of NO production and external
stimulation in determining the eventual pro- or anti-apoptotic role of NO.
This model was taken from the CellML repository
and automatically converted to SBML.
The original model was:
Bagci EZ, Vodovotz Y, Billiar TR, Ermentrout B, Bahar I. (2008) - version=1.0
The original CellML model was created by:
Wendy Kang
wkan014@aucklanduni.ac.nz
The University of Auckland
This model originates from BioModels Database: A Database of Annotated Published Models (http://www.ebi.ac.uk/biomodels/). It is copyright (c) 2005-2011 The BioModels.net Team.
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.
In summary, you are entitled to use this encoded model in absolutely any manner you deem suitable, verbatim, or with modification, alone or embedded it in a larger context, redistribute it, commercially or not, in a restricted way or not..
To cite BioModels Database, please use: Li C, Donizelli M, Rodriguez N, Dharuri H, Endler L, Chelliah V, Li L, He E, Henry A, Stefan MI, Snoep JL, Hucka M, Le Novère N, Laibe C (2010) BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models. BMC Syst Biol., 4:92.
2005-01-01 | MODEL1006230064 | BioModels
Project description:This a model from the article:
Computational insights on the competing effects of nitric oxide in regulating
apoptosis.
Bagci EZ, Vodovotz Y, Billiar TR, Ermentrout B, Bahar I. PLoS One
2008 May 28;3(5):e2249 18509469
,
Abstract:
Despite the establishment of the important role of nitric oxide (NO) on
apoptosis, a molecular-level understanding of the origin of its dichotomous pro-
and anti-apoptotic effects has been elusive. We propose a new mathematical model
for simulating the effects of nitric oxide (NO) on apoptosis. The new model
integrates mitochondria-dependent apoptotic pathways with NO-related reactions,
to gain insights into the regulatory effect of the reactive NO species N(2)O(3),
non-heme iron nitrosyl species (FeL(n)NO), and peroxynitrite (ONOO(-)). The
biochemical pathways of apoptosis coupled with NO-related reactions are
described by ordinary differential equations using mass-action kinetics. In the
absence of NO, the model predicts either cell survival or apoptosis (a bistable
behavior) with shifts in the onset time of apoptotic response depending on the
strength of extracellular stimuli. Computations demonstrate that the relative
concentrations of anti- and pro-apoptotic reactive NO species, and their
interplay with glutathione, determine the net anti- or pro-apoptotic effects at
long time points. Interestingly, transient effects on apoptosis are also
observed in these simulations, the duration of which may reach up to hours,
despite the eventual convergence to an anti-apoptotic state. Our computations
point to the importance of precise timing of NO production and external
stimulation in determining the eventual pro- or anti-apoptotic role of NO.
This model was taken from the CellML repository
and automatically converted to SBML.
The original model was:
Bagci EZ, Vodovotz Y, Billiar TR, Ermentrout B, Bahar I. (2008) - version=1.0
The original CellML model was created by:
Wendy Kang
wkan014@aucklanduni.ac.nz
The University of Auckland
This model originates from BioModels Database: A Database of Annotated Published Models (http://www.ebi.ac.uk/biomodels/). It is copyright (c) 2005-2011 The BioModels.net Team.
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.
In summary, you are entitled to use this encoded model in absolutely any manner you deem suitable, verbatim, or with modification, alone or embedded it in a larger context, redistribute it, commercially or not, in a restricted way or not..
To cite BioModels Database, please use: Li C, Donizelli M, Rodriguez N, Dharuri H, Endler L, Chelliah V, Li L, He E, Henry A, Stefan MI, Snoep JL, Hucka M, Le Novère N, Laibe C (2010) BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models. BMC Syst Biol., 4:92.
2005-01-01 | MODEL1006230026 | BioModels
Project description:The hepatitis E virus (HEV), a non enveloped RNA virus, causes viral hepatitis. The viral open reading frame 2 (ORF2) protein represents the capsid protein of HEV which is known to cause endoplasmic reticulum stress in ORF2 expressing cells. The initiation of endoplasmic reticulum stress induced apoptosis mainly involves the transcriptional activation of pro-apoptotic gene CHOP which will further trigger the major apoptotic pathways. However, the activation of CHOP by ORF2 protein in this study does not induce apoptotic markers such as Bax translocation to mitochondria. We have used the Affymetrix microarray platform to screen the pro-apoptotic effects induced by the expression of ORF2 protein in human hepatic cell lines (Huh7). The Huh7 cells were transduced either with recombinant adenovirus encoding the HEV ORF2 (Ad-ORF2) or an adenovirus encoding the green fluorescent protein (Ad-GFP). The array results consistently showed an ORF2 specific induction of mRNA corresponding to the chaperones Hsp72, Hsp70B’ and co-chaperone Hsp40. These studies provide further mechanisms of the ER stress mediated pro apoptotic effects caused by the ORF2 protein and its potential role for the activation of anti-apoptotic activity of the host cell.
2012-12-01 | GSE29061 | GEO
Project description:In this study we provide evidence on potential mechanisms involved in H2S mediated protection against VILI. H2S down-regulates genes that are involved in oxidative stress and pro-inflammatory cell responses. H2S regulates ECM remodelling, a mechanism which may contribute to H2S-mediated lung protection. In addition, H2S inhalation activates anti-apoptotic and anti-inflammatory genes, and genes controlling the vascular permeability. The functional relevance of Atf3 underscores the potential of H2S to limit lung injury. We utilized a microarray approach for large scale analysis of target genes in order to elucidate the therapeutic effects of H2S in VILI. This study demonstrates the influence of supplemental H2S on gene expression in a model of VILI. In addition to describing the genes differentially regulated in VILI, the present study focused on newly identified H2S target genes within several functional groups, including anti-inflammatory and anti-apoptotic pathways, regulation of extracellular matrix (ECM) remodelling and angiogenesis. Gene expression analysis of control group, allowed to breathe spontaneously synthetic air and mice ventilated with synthetic air or synthetic air with 80 ppm H2S for 6 hours.
2014-06-03 | E-GEOD-58169 | biostudies-arrayexpress
Project description:The chromosomal translocation t(11;14)(q13;q32) leading to cyclin-D1 over-expression plays an essential role in the development of mantle cell lymphoma (MCL), an aggressive tumor that remains incurable with current therapies. Cyclin-D1 has been postulated as an effective therapeutic target, but its evaluation has been hampered by our incomplete understanding of its oncogenic functions and by the lack of valid MCL murine models. To address these issues, we generated a cyclin-D1-driven mouse model whereby cyclin-D1 expression can be externally regulated. These mice developed lymphomas capable of recapitulating most features of human MCL. We found that cyclin-D1 inactivation was not sufficient to induce lymphoma regression in vivo. However, using a combination of in vitro and in vivo assays, we identified a novel pro-survival cyclin-D1 function in MCL cells. Specifically, we demonstrate that cyclin-D1 sequestrates the pro-apoptotic protein BAX, thereby favoring BCL2 anti-apoptotic function. Accordingly, cyclin-D1 inhibition sensitized the lymphoma cells to apoptosis through BAX release. Thus, genetic or pharmacologic targeting of cyclin-D1 combined with a pro-apoptotic BH3 mimetic synergistically killed murine lymphomas and human MCL cells. Our study identifies a novel role of cyclin-D1 in deregulating apoptosis and highlights the potential benefit of simultaneously targeting cyclin-D1 and survival pathways in patients with MCL. Dose response involving 20 samples. Two replicates for each cell line, 4 cell lines sensitive to ABT-737 and 6 cell lines resistant to ABT-737. Mantel cell lymphoma cell lines sensitive to ABT-737 vs. Mantel cell lymphoma cell lines resistant to ABT-737
2011-07-01 | E-GEOD-25613 | biostudies-arrayexpress
Project description:The DNA damage response network modulates a wide array of signaling pathways, including DNA repair, cell cycle checkpoints, apoptotic pathways and numerous stress signals. The ATM protein kinase, functionally missing in patients with the human genetic disorder ataxia-telangiectasia (A-T), is a master regulator of this network when the inducing DNA lesions are double strand breaks. The ATM gene is also frequently mutated in sporadic cancers of lymphoid origin. Here, we applied a functional genomics approach that combines gene expression profiling and computational promoter analysis to obtain global dissection of the transcriptional response to ionizing radiation (IR) in murine lymphoid tissue. Cluster analysis revealed six major expression patterns in the data. Prominent among them was a gene cluster that contained dozens of genes whose response to irradiation was Atm-dependent. Computational analysis identified significant enrichment of the binding site signatures of the transcription factors NF-kB and p53 among promoters of these genes, pointing to the major role of these two transcription factors in mediating the Atm-dependent transcriptional response in the irradiated lymphoid tissue. Examination of the response showed that pro- and anti-apoptotic signals were simultaneously induced, with the pro-apoptotic pathway mediated by p53, and the pro-survival pathway by NF-kB. These findings further elucidate the molecular network induced by IR and have implications for cancer management as they suggest that a combined treatment that restores the p53-mediated apoptotic arm while blocking the NF-kB-mediated pro-survival arm could be most successful in increasing the radiosensitivity of lymphoid tumors.
2007-12-04 | E-GEOD-2118 | biostudies-arrayexpress