ArticleScientific reports2022
Dynamic modeling of Nrf2 pathway activation in liver cells after toxicant exposure.
Article in Scientific reports, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 24 citations in OpenAlex.
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- Systematic comparison of temporal hepatotoxicant-induced gene network responses across 3 liver test systems.Toxicological sciences : an official journal of the Society of Toxicology · 2026Article
- Melatonin Targets Mitochondrial Redox Homeostasis: Optimizing the Intracellular Microenvironment.International journal of molecular sciences · 2026Review
- Age-related effects of high protein diet on rat liver and kidney.Irish journal of medical science · 2026Article
- Integrative Omics Defines Metabolic Biomarkers and Genetic Regulatory Mechanisms of Mortality Risk.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Trigonelline activates NRF2 and awakens dormant ovarian follicles to promote pregnancy in aging mice.iScience · 2025Article
- Computational modelling identifies primary mediators of crosstalk between DNA damage and oxidative stress responses.PLoS computational biology · 2025Article
- Novel anti-inflammatory properties of mannose oligosaccharides in the treatment of inflammatory bowel disease via LGALS3 modulation.NPJ biofilms and microbiomes · 2025Article
- Acute COVID-19 and LongCOVID syndrome - molecular implications for therapeutic strategies - review.Frontiers in immunology · 2025Review
- Understanding chronic inflammation: couplings between cytokines, ROS, NO, CaFrontiers in immunology · 2025Review
- Integrating Time-ResolvedEnvironmental science & technology · 2024Article
- Gut Microbiota and Metabolic Dysfunction-Associated Steatotic Liver Disease.Antioxidants (Basel, Switzerland) · 2024Review
- Advances in drug-induced liver injury research: in vitro models, mechanisms, omics and gene modulation techniques.Cell & bioscience · 2024Review
- Contributing roles of mitochondrial dysfunction and hepatocyte apoptosis in liver diseases through oxidative stress, post-translational modifications, inflammation, and intestinal barrier dysfunction.Cellular and molecular life sciences : CMLS · 2024Review
- A Review of the Potential of Nuclear Factor [Erythroid-Derived 2]-like 2 Activation in Autoimmune Diseases.Brain sciences · 2023Review
- Signal amplification in the KEAP1-NRF2-ARE antioxidant response pathway.Redox biology · 2022Review
- Liver Regeneration: Changes in Oxidative Stress, Immune System, Cytokines, and Epigenetic Modifications Associated with Aging.Oxidative medicine and cellular longevity · 2022Review
Corrections and comments
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Authors and funding
13 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cells are exposed to oxidative stress and reactive metabolites every day. The Nrf2 signaling pathway responds to oxidative stress by upregulation of antioxidants like glutathione (GSH) to compensate the stress insult and re-establish homeostasis. Although mechanisms describing the interaction between the key pathway constituents Nrf2, Keap1 and p62 are widely reviewed and discussed in literature, quantitative dynamic models bringing together these mechanisms with time-resolved data are limited. Here, we present an ordinary differential equation (ODE) based dynamic model to describe the dynamic response of Nrf2, Keap1, Srxn1 and GSH to oxidative stress caused by the soft-electrophile diethyl maleate (DEM). The time-resolved data obtained by single-cell confocal microscopy of green fluorescent protein (GFP) reporters and qPCR of the Nrf2 pathway components complemented with siRNA knock down experiments, is accurately described by the calibrated mathematical model. We show that the quantitative model can describe the activation of the Nrf2 pathway by compounds with a different mechanism of activation, including drugs which are known for their ability to cause drug induced liver-injury (DILI) i.e., diclofenac (DCF) and omeprazole (OMZ). Finally, we show that our model can reveal differences in the processes leading to altered activation dynamics amongst DILI inducing drugs.
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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.