Data from: Polycyclic aromatic hydrocarbons can trigger hepatocyte release of extracellular vesicles by various mechanisms of action depending on their affinity for the aryl hydrocarbon receptor.
Data files
Jul 11, 2019 version files 8.58 MB
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Supplementary Table S1.doc
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Jul 11, 2019 version files 17.17 MB
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Figure S1.tif
902.20 KB
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Figure S2.tif
2.32 MB
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Figure S3.tif
859.43 KB
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Figure S4.tif
864.39 KB
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Figure S5.tif
749.74 KB
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Figure S6.tif
848.31 KB
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Figure S7.tif
903.84 KB
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Figure S8.tif
906.28 KB
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Supplementary Table S1.doc
35.84 KB
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Supplementary Table S2.doc
65.54 KB
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Supplementary Table S3.doc
48.13 KB
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Supplementary Table S4.doc
37.89 KB
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Supplementary Table S5.doc
38.91 KB
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. EVs 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 three 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 three 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 (CAR), 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.