Effects of benzo[k]fluoranthene, a potent AhR ligand, on proteosynthesis and glucose metabolic regulators/effectors in liver cell models

PETRÁŠ, Jiří, Martina KARASOVÁ, Anna LNĚNIČKOVÁ, Miroslav MACHALA, Pavlína ŠIMEČKOVÁ and Jan VONDRÁČEK. Effects of benzo[k]fluoranthene, a potent AhR ligand, on proteosynthesis and glucose metabolic regulators/effectors in liver cell models. In Květinův Den 2023. 2023. ISBN 978-80-280-0305-0.

Basic information

• Original name: Effects of benzo[k]fluoranthene, a potent AhR ligand, on proteosynthesis and glucose metabolic regulators/effectors in liver cell models
• Authors: PETRÁŠ, Jiří, Martina KARASOVÁ, Anna LNĚNIČKOVÁ, Miroslav MACHALA, Pavlína ŠIMEČKOVÁ and Jan VONDRÁČEK.
• Edition: Květinův Den 2023, 2023.

Other information

• Original language: English
• Type of outcome: Presentations at conferences
• Field of Study: 10511 Environmental sciences
• Country of publisher: Czech Republic
• Confidentiality degree: is not subject to a state or trade secret
• WWW: URL
• Organization unit: Faculty of Science
• ISBN: 978-80-280-0305-0
• Keywords in English: Aryl Hydrocarbon Receptor, Hepatocytes, Metabolism, Pollutants

Abstract

Polyaromatic hydrocarbons (PAHs) are an important group of environmental pollutants produced by industry, road traffic or local heating. These substances have been primarily studied as carcinogens; however, their spectrum of toxic effects appears to be much larger and may include also endocrine or metabolic disruption. Benzo(k)fluoranthene (BkF) is a toxic PAH associated with airborne particulate pollution (PM) that is a potent ligand of the aryl hydrocarbon receptor (AhR). This transcription factor is a key regulator of the cytochrome P450 family 1 enzymes, which then metabolize BkF, thus leading both to its detoxification and production of various toxic metabolites, which may further impact various signaling pathways within cells, and thus modulate toxic consequences of aberrant AhR activation. Here, we evaluated some selected metabolic processes in human liver cells, using several liver cell lines as models for this tissue. We analyzed the expression of genes involved in glucose metabolism/transport, effects of BkF on glucose release and the impact of BkF on protein translation in target cells. Our results indicate that BkF can have multiple effects on cellular metabolism of human hepatocyte cell models, including a reduction in the ability to release glucose into cell culture medium, reduced gene expression of a major initiator of gluconeogenesis and glucose transporter, as well as a decrease of an overall translation rate. This indicates that some PAHs acting as efficient AhR ligands may deregulate energy metabolism in human liver cell models. Further attention should be paid to the impact of PAHs (and structurally-related environmental contaminants) on metabolic processes within the liver, as they could be linked with the development of metabolic disorders in individuals exposed to high levels of these pollutants for extended periods of time. [This study was supported by the Czech Science Foundation, project no. 21-00533S.]