CYTOTOXICITY AND ARYL HYDROCARBON RECEPTOR–MEDIATED ACTIVITY OF N-HETEROCYCLIC POLYCYCLIC AROMATIC HYDROCARBONS: STRUCTURE–ACTIVITY RELATIONSHIPS

2006 ◽  
Vol 25 (5) ◽  
pp. 1291 ◽  
Author(s):  
Iva Sovadinová ◽  
Luděk Bláha ◽  
Jaroslav Janošek ◽  
Klára Hilscherová ◽  
John P. Giesy ◽  
...  
Keyword(s):  
Polycyclic Aromatic Hydrocarbons ◽  
Aryl Hydrocarbon Receptor ◽  
Aromatic Hydrocarbons ◽  
Structure Activity Relationships ◽  
Aryl Hydrocarbon ◽  
Structure Activity ◽  
Polycyclic Aromatic

Polycyclic Aromatic Hydrocarbons Can Trigger Hepatocyte Release of Extracellular Vesicles by Various Mechanisms of Action Depending on Their Affinity for the Aryl Hydrocarbon Receptor

2019 ◽  
Vol 171 (2) ◽  
pp. 443-462 ◽  
Author(s):  
Nettie van Meteren ◽  
Dominique Lagadic-Gossmann ◽  
Martine Chevanne ◽  
Isabelle Gallais ◽  
Dimitri Gobart ◽  
...  
Keyword(s):  
Cell Death ◽  
Transcription Factor ◽  
Polycyclic Aromatic Hydrocarbons ◽  
Cell Membrane ◽  
Aryl Hydrocarbon Receptor ◽  
Extracellular Vesicles ◽  
Aromatic Hydrocarbons ◽  
Aryl Hydrocarbon ◽  
Polycyclic Aromatic ◽  
Cell Membrane Fluidity

Abstract Extracellular vesicles (EVs) are membrane-enclosed nanostructures released by cells into the extracellular environment. As major actors of physiological intercellular communication, they have been shown to be pathogenic mediators of several liver diseases. Extracellular vesicles also appear to be potential actors of drug-induced liver injury but nothing is known concerning environmental pollutants. We aimed to study the impact of polycyclic aromatic hydrocarbons (PAHs), major contaminants, on hepatocyte-derived EV production, with a special focus on hepatocyte death. Three PAHs were selected, based on their presence in food and their affinity for the aryl hydrocarbon receptor (AhR): benzo[a]pyrene (BP), dibenzo[a,h]anthracene (DBA), and pyrene (PYR). Treatment of primary rat and WIF-B9 hepatocytes by all 3 PAHs increased the release of EVs, mainly comprised of exosomes, in parallel with modifying exosome protein marker expression and inducing apoptosis. Moreover, PAH treatment of rodents for 3 months also led to increased EV levels in plasma. The EV release involved CYP metabolism and the activation of the transcription factor, the AhR, for BP and DBA and another transcription factor, the constitutive androstane receptor, for PYR. Furthermore, all PAHs increased cholesterol levels in EVs but only BP and DBA were able to reduce the cholesterol content of total cell membranes. All cholesterol changes very likely participated in the increase in EV release and cell death. Finally, we studied changes in cell membrane fluidity caused by BP and DBA due to cholesterol depletion. Our data showed increased cell membrane fluidity, which contributed to hepatocyte EV release and cell death.

The role of functional human aryl hydrocarbon receptor in estrogenicity of polycyclic aromatic hydrocarbons

2017 ◽  
Vol 280 ◽  
pp. S85-S86
Author(s):  
Martina Hyzdalova ◽  
Jakub Pivnicka ◽  
Ondrej Zapletal ◽  
Gerardo Vazquez-Gomez ◽  
Jason Matthews ◽  
...  
Keyword(s):  
Polycyclic Aromatic Hydrocarbons ◽  
Aryl Hydrocarbon Receptor ◽  
Aromatic Hydrocarbons ◽  
Aryl Hydrocarbon ◽  
Polycyclic Aromatic

scholarly journals Aryl Hydrocarbon Receptor-Dependent Metabolism Plays a Significant Role in Estrogen-Like Effects of Polycyclic Aromatic Hydrocarbons on Cell Proliferation

2018 ◽  
Vol 165 (2) ◽  
pp. 447-461 ◽  
Author(s):  
Martina Hýžd′alová ◽  
Jakub Pivnička ◽  
Ondřej Zapletal ◽  
Gerardo Vázquez-Gómez ◽  
Jason Matthews ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Polycyclic Aromatic Hydrocarbons ◽  
Aryl Hydrocarbon Receptor ◽  
Significant Role ◽  
Aromatic Hydrocarbons ◽  
Aryl Hydrocarbon ◽  
Polycyclic Aromatic

scholarly journals Antioxidant Functions of the Aryl Hydrocarbon Receptor

2016 ◽  
Vol 2016 ◽  
pp. 1-10 ◽  
Author(s):  
Cornelia Dietrich
Keyword(s):  
Polycyclic Aromatic Hydrocarbons ◽  
Aryl Hydrocarbon Receptor ◽  
Aromatic Hydrocarbons ◽  
Transcriptional Activation ◽  
Antioxidant Response ◽  
Protective Role ◽  
Helix Loop Helix ◽  
Aryl Hydrocarbon ◽  
Polycyclic Aromatic

The aryl hydrocarbon receptor (AhR) is a transcription factor belonging to the basic helix-loop-helix/PER-ARNT-SIM family. It is activated by a variety of ligands, such as environmental contaminants like polycyclic aromatic hydrocarbons or dioxins, but also by naturally occurring compounds and endogenous ligands. Binding of the ligand leads to dimerization of the AhR with aryl hydrocarbon receptor nuclear translocator (ARNT) and transcriptional activation of several xenobiotic phase I and phase II metabolizing enzymes. It is generally accepted that the toxic responses of polycyclic aromatic hydrocarbons, dioxins, and structurally related compounds are mediated by activation of the AhR. A multitude of studies indicate that the AhR operates beyond xenobiotic metabolism and exerts pleiotropic functions. Increasing evidence points to a protective role of the AhR against carcinogenesis and oxidative stress. Herein, I will highlight data demonstrating a causal role of the AhR in the antioxidant response and present novel findings on potential AhR-mediated antioxidative mechanisms.

scholarly journals Polycyclic aromatic hydrocarbons (PAHs) present in ambient urban dust drive proinflammatory T cell and dendritic cell responses via the aryl hydrocarbon receptor (AHR) in vitro

PLoS ONE ◽  
2018 ◽  
Vol 13 (12) ◽  
pp. e0209690 ◽  
Author(s):  
Chelsea A. O’Driscoll ◽  
Madeline E. Gallo ◽  
Erica J. Hoffmann ◽  
John H. Fechner ◽  
James J. Schauer ◽  
...  
Keyword(s):  
Polycyclic Aromatic Hydrocarbons ◽  
T Cell ◽  
Dendritic Cell ◽  
Aryl Hydrocarbon Receptor ◽  
Aromatic Hydrocarbons ◽  
Urban Dust ◽  
Cell Responses ◽  
Aryl Hydrocarbon ◽  
Polycyclic Aromatic
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