ArticlePloS one2011
Modeling the TNFα-induced apoptosis pathway in hepatocytes.
Article in PloS one, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 38 citations in OpenAlex.
- Modulating the dynamics of NFκB and PI3K enhances the ensemble-level TNFR1 signaling mediated apoptotic response.NPJ systems biology and applications · 2023Article
- Concepts in Boolean network modeling: What do they all mean?Computational and structural biotechnology journal · 2020Review
- IL-1β and TNFα Differentially Influence NF-κB Activity and FasL-Induced Apoptosis in Primary Murine Hepatocytes During LPS-Induced Inflammation.Frontiers in physiology · 2019Article
- IL-1β Promotes a New Function of DNase I as a Transcription Factor for the Fas Receptor Gene.Frontiers in cell and developmental biology · 2018Article
- Toxicity and efficiency study of plant extracts-based bleaching agents.Clinical oral investigations · 2017Article
- Knowledge-guided fuzzy logic modeling to infer cellular signaling networks from proteomic data.Scientific reports · 2016Article
- An Agent-Based Model of a Hepatic Inflammatory Response to Salmonella: A Computational Study under a Large Set of Experimental Data.PloS one · 2016Article
- Discovery of Drug Synergies in Gastric Cancer Cells Predicted by Logical Modeling.PLoS computational biology · 2015Article
- Nonlethal dose of silver nanoparticles attenuates TNF-α-induced hepatic epithelial cell death through HSP70 overexpression.American journal of physiology. Cell physiology · 2015Article
- Article
- Association of heme oxygenase 1 with the restoration of liver function after damage in murine malaria by Plasmodium yoelii.Infection and immunity · 2014Article
- Primary hepatocytes and their cultures in liver apoptosis research.Archives of toxicology · 2014Review
- Mathematical modeling of the Phoenix Rising pathway.PLoS computational biology · 2014Article
- Interleukin-1β enhances FasL-induced caspase-3/-7 activity without increasing apoptosis in primary mouse hepatocytes.PloS one · 2014Article
- Nucling, a novel protein associated with NF-κB, regulates endotoxin-induced apoptosis in vivo.Journal of biochemistry · 2013Article
- Soluble TNF-alpha-receptors I are prognostic markers in TIPS-treated patients with cirrhosis and portal hypertension.PloS one · 2013Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The proinflammatory cytokine TNFα fails to provoke cell death in isolated hepatocytes but has been implicated in hepatocyte apoptosis during liver diseases associated with chronic inflammation. Recently, we showed that TNFα is able to sensitize primary murine hepatocytes cultured on collagen to Fas ligand-induced apoptosis and presented a mathematical model of the sensitizing effect. Here, we analyze how TNFα induces apoptosis in combination with the transcriptional inhibitor actinomycin D (ActD). Accumulation of reactive oxygen species (ROS) in response to TNFR activation turns out to be critical for sustained activation of JNK which then triggers mitochondrial pathway-dependent apoptosis. In addition, the amount of JNK is strongly upregulated in a ROS-dependent way. In contrast to TNFα plus cycloheximide no cFLIP degradation is observed suggesting a different apoptosis pathway in which the Itch-mediated cFLIP degradation and predominantly caspase-8 activation is not involved. Time-resolved data of the respective pro- and antiapoptotic factors are obtained and subjected to mathematical modeling. On the basis of these data we developed a mathematical model which reproduces the complex interplay regulating the phosphorylation status of JNK and generation of ROS. This model was fully integrated with our model of TNFα/Fas ligand sensitizing as well as with a published NF-κB-model. The resulting comprehensive model delivers insight in the dynamical interplay between the TNFα and FasL pathways, NF-κB and ROS and gives an example for successful model integration.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.