ArticleCellular signalling2019
Hepatic signalling disruption by pollutant Polychlorinated biphenyls in steatohepatitis.
Article in Cellular signalling, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
15 citing papers in PubMed, 20 citations in OpenAlex.
- Review
- Sex-dependent modulation of PCB-mediated toxicity from a proteomic and microbiome perspective.Scientific reports · 2025Article
- Multiomics Analysis of PCB126's Effect on a Mouse Chronic-Binge Alcohol Feeding Model.Environmental health perspectives · 2024Article
- Endocrine disrupting chemicals: A promoter of non-alcoholic fatty liver disease.Frontiers in public health · 2023Review
- Polychlorinated biphenyls alter hepatic m6A mRNA methylation in a mouse model of environmental liver disease.Environmental research · 2023Article
- Obesity II: Establishing causal links between chemical exposures and obesity.Biochemical pharmacology · 2022Review
- Circulating MicroRNAs, Polychlorinated Biphenyls, and Environmental Liver Disease in the Anniston Community Health Survey.Environmental health perspectives · 2022Article
- CK2 Regulation: Perspectives in 2021.Biomedicines · 2021Review
- Effect of Epidermal Growth Factor Treatment and Polychlorinated Biphenyl Exposure in a Dietary-Exposure Mouse Model of Steatohepatitis.Environmental health perspectives · 2021Article
- Combined exposure to polychlorinated biphenyls and high-fat diet modifies the global epitranscriptomic landscape in mouse liver.Environmental epigenetics · 2021Article
- Dioxin-like and non-dioxin-like PCBs differentially regulate the hepatic proteome and modify diet-induced nonalcoholic fatty liver disease severity.Medicinal chemistry research : an international journal for rapid communications on design and mechanisms of action of biologically active agents · 2020Article
- Constitutive androstane receptor mediates PCB-induced disruption of retinoid homeostasis.Toxicology and applied pharmacology · 2019Article
- Mechanisms of Environmental Contributions to Fatty Liver Disease.Current environmental health reports · 2019Review
- Proteomic Analysis Reveals Novel Mechanisms by Which Polychlorinated Biphenyls Compromise the Liver Promoting Diet-Induced Steatohepatitis.Journal of proteome research · 2019Article
- Polychlorinated Biphenyls and Nonalcoholic Fatty Liver Disease.Current opinion in toxicology · 2019Article
Corrections and comments
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
backgroundPolychlorinated biphenyl-mediated steatohepatitis has been shown to be due in part to inhibition of epidermal growth factor receptor (EGFR) signalling. EGFR signalling regulates many facets of hepatocyte function, but it is unclear which other kinases and pathways are involved in the development of toxicant-associated steatohepatitis (TASH).
methodsComparative hepatic phosphoproteomic analysis was used to identify which kinases were affected by either PCB exposure (Aroclor 1260 mixture), high fat diet (HFD), or their interaction in a chronic exposure model of TASH. Cellular assays and western blot analysis were used to validate the phosphoproteomic findings.
results1760 unique phosphorylated peptides were identified and of those 588 were significantly different. PCB exposure and dietary interaction promoted a near 25% reduction of hepatic phospho-peptides. Leptin and insulin signalling were pathways highly affected by PCB exposure and liver necrosis was a pathologic ontology over represented due to interaction between PCBs and a HFD. Casein kinase 2 (CK2), Extracellular regulated kinase (ERK), Protein kinase B (AKT), and Cyclin dependent kinase (CDK) activity were demonstrated to be downregulated after PCB exposure and this downregulation was exacerbated with a HFD. PCB exposure led to a loss of hepatic CK2 subunit expression limiting CK2 kinase activity and negatively regulating caspase-3 (CASP3). PCBs promoted secondary necrosis in vitro validating the latter observation. The loss of hepatic phosphoprotein signalling appeared to be due to decreased signal transduction rather than phosphatase upregulation.
conclusionsPCBs are signal disrupting chemicals that promote secondary necrosis through affecting a myriad of liver processes including metabolism and cellular maintenance. PCB exposure, particularly with interaction with a HFD greatly down-regulates the hepatic kinome. More data are needed on signalling disruption and its impact on liver health.
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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 Socratic graph.