The Effect of Plastic-Related Compounds on Transcriptome-Wide Gene Expression on CYP2C19-Overexpressing HepG2 Cells
- Publication type:
- Journal article
- Metadata:
-
- Autoren
- Matteo Rosellini
- Alicia Schulze
- Ejlal A Omer
- Nadeen T Ali
- Federico Marini
- Jan-Heiner Kuepper
- Thomas Efferth
- Autoren-URL
- https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=fis-test-1&SrcAuth=WosAPI&KeyUT=WOS:001055731000001&DestLinkType=FullRecord&DestApp=WOS_CPL
- DOI
- 10.3390/molecules28165952
- eISSN
- 1420-3049
- Externe Identifier
- Clarivate Analytics Document Solution ID: Q2FQ6
- PubMed Identifier: 37630204
- Ausgabe der Veröffentlichung
- 16
- Zeitschrift
- MOLECULES
- Schlüsselwörter
- cytotoxicity
- ecotoxicity
- hepatotoxicity
- microplastic
- RNA sequencing
- Artikelnummer
- ARTN 5952
- Datum der Veröffentlichung
- 2023
- Status
- Published
- Titel
- The Effect of Plastic-Related Compounds on Transcriptome-Wide Gene Expression on CYP2C19-Overexpressing HepG2 Cells
- Sub types
- Article
- Ausgabe der Zeitschrift
- 28
Data source: Web of Science (Lite)
- Other metadata sources:
-
- Abstract
- <jats:p>In recent years, plastic and especially microplastic in the oceans have caused huge problems to marine flora and fauna. Recently, such particles have also been detected in blood, breast milk, and placenta, underlining their ability to enter the human body, presumably via the food chain and other yet-unknown mechanisms. In addition, plastic contains plasticizers, antioxidants, or lubricants, whose impact on human health is also under investigation. At the cellular level, the most important enzymes involved in the metabolism of xenobiotic compounds are the cytochrome P450 monooxygenases (CYPs). Despite their extensive characterization in the maintenance of cellular balance, their interactions with plastic and related products are unexplored. In this study, the possible interactions between several plastic-related compounds and one of the most important cytochromes, CYP2C19, were analyzed. By applying virtual compound screening and molecular docking to more than 1000 commercially available plastic-related compounds, we identified candidates that are likely to interact with this protein. A growth inhibition assay confirmed their cytotoxic activity on a CYP2C19-transfected hepatic cell line. Subsequently, we studied the effect of the selected compounds on the transcriptome-wide gene expression level by conducting RNA sequencing. Three candidate molecules were identified, i.e., 2,2′-methylene bis(6-tert-butyl-4-methylphenol), 1,1-bis(3,5-di-tert-butyl-2-hydroxyphenyl) ethane, and 2,2′-methylene bis(6-cyclohexyl-4-methylphenol)), which bound with a high affinity to CYP2C19 in silico. They exerted a profound cytotoxicity in vitro and interacted with several metabolic pathways, of which the ‘cholesterol biosynthesis process’ was the most affected. In addition, other affected pathways involved mitosis, DNA replication, and inflammation, suggesting an increase in hepatotoxicity. These results indicate that plastic-related compounds could damage the liver by affecting several molecular pathways.</jats:p>
- Autoren
- Matteo Rosellini
- Alicia Schulze
- Ejlal A Omer
- Nadeen T Ali
- Federico Marini
- Jan-Heiner Küpper
- Thomas Efferth
- DOI
- 10.3390/molecules28165952
- eISSN
- 1420-3049
- Ausgabe der Veröffentlichung
- 16
- Zeitschrift
- Molecules
- Sprache
- en
- Online publication date
- 2023
- Paginierung
- 5952 - 5952
- Status
- Published online
- Herausgeber
- MDPI AG
- Herausgeber URL
- http://dx.doi.org/10.3390/molecules28165952
- Datum der Datenerfassung
- 2023
- Titel
- The Effect of Plastic-Related Compounds on Transcriptome-Wide Gene Expression on CYP2C19-Overexpressing HepG2 Cells
- Ausgabe der Zeitschrift
- 28
Data source: Crossref
- Abstract
- In recent years, plastic and especially microplastic in the oceans have caused huge problems to marine flora and fauna. Recently, such particles have also been detected in blood, breast milk, and placenta, underlining their ability to enter the human body, presumably via the food chain and other yet-unknown mechanisms. In addition, plastic contains plasticizers, antioxidants, or lubricants, whose impact on human health is also under investigation. At the cellular level, the most important enzymes involved in the metabolism of xenobiotic compounds are the cytochrome P450 monooxygenases (CYPs). Despite their extensive characterization in the maintenance of cellular balance, their interactions with plastic and related products are unexplored. In this study, the possible interactions between several plastic-related compounds and one of the most important cytochromes, CYP2C19, were analyzed. By applying virtual compound screening and molecular docking to more than 1000 commercially available plastic-related compounds, we identified candidates that are likely to interact with this protein. A growth inhibition assay confirmed their cytotoxic activity on a CYP2C19-transfected hepatic cell line. Subsequently, we studied the effect of the selected compounds on the transcriptome-wide gene expression level by conducting RNA sequencing. Three candidate molecules were identified, i.e., 2,2'-methylene bis(6-tert-butyl-4-methylphenol), 1,1-bis(3,5-di-tert-butyl-2-hydroxyphenyl) ethane, and 2,2'-methylene bis(6-cyclohexyl-4-methylphenol)), which bound with a high affinity to CYP2C19 in silico. They exerted a profound cytotoxicity in vitro and interacted with several metabolic pathways, of which the 'cholesterol biosynthesis process' was the most affected. In addition, other affected pathways involved mitosis, DNA replication, and inflammation, suggesting an increase in hepatotoxicity. These results indicate that plastic-related compounds could damage the liver by affecting several molecular pathways.
- Addresses
- Department of Pharmaceutical Biology, Institute of Pharmaceutical and Biomedical Sciences, Johannes Gutenberg University, Staudinger Weg 5, 55128 Mainz, Germany.
- Autoren
- Matteo Rosellini
- Alicia Schulze
- Ejlal A Omer
- Nadeen T Ali
- Federico Marini
- Jan-Heiner Küpper
- Thomas Efferth
- DOI
- 10.3390/molecules28165952
- eISSN
- 1420-3049
- Externe Identifier
- PubMed Identifier: 37630204
- PubMed Central ID: PMC10459118
- Funding acknowledgements
- Deutsche Forschungsgemeinschaft: GRK 2015/2
- Open access
- true
- ISSN
- 1420-3049
- Ausgabe der Veröffentlichung
- 16
- Zeitschrift
- Molecules (Basel, Switzerland)
- Schlüsselwörter
- Humans
- Plastics
- Pregnancy
- Female
- Hep G2 Cells
- Transcriptome
- Molecular Docking Simulation
- Cytochrome P-450 CYP2C19
- Sprache
- eng
- Medium
- Electronic
- Online publication date
- 2023
- Open access status
- Open Access
- Paginierung
- 5952
- Datum der Veröffentlichung
- 2023
- Status
- Published
- Publisher licence
- CC BY
- Datum der Datenerfassung
- 2023
- Titel
- The Effect of Plastic-Related Compounds on Transcriptome-Wide Gene Expression on CYP2C19-Overexpressing HepG2 Cells.
- Sub types
- research-article
- Journal Article
- Ausgabe der Zeitschrift
- 28
Files
https://www.mdpi.com/1420-3049/28/16/5952/pdf?version=1691501412 https://europepmc.org/articles/PMC10459118?pdf=render
Data source: Europe PubMed Central
- Abstract
- In recent years, plastic and especially microplastic in the oceans have caused huge problems to marine flora and fauna. Recently, such particles have also been detected in blood, breast milk, and placenta, underlining their ability to enter the human body, presumably via the food chain and other yet-unknown mechanisms. In addition, plastic contains plasticizers, antioxidants, or lubricants, whose impact on human health is also under investigation. At the cellular level, the most important enzymes involved in the metabolism of xenobiotic compounds are the cytochrome P450 monooxygenases (CYPs). Despite their extensive characterization in the maintenance of cellular balance, their interactions with plastic and related products are unexplored. In this study, the possible interactions between several plastic-related compounds and one of the most important cytochromes, CYP2C19, were analyzed. By applying virtual compound screening and molecular docking to more than 1000 commercially available plastic-related compounds, we identified candidates that are likely to interact with this protein. A growth inhibition assay confirmed their cytotoxic activity on a CYP2C19-transfected hepatic cell line. Subsequently, we studied the effect of the selected compounds on the transcriptome-wide gene expression level by conducting RNA sequencing. Three candidate molecules were identified, i.e., 2,2'-methylene bis(6-tert-butyl-4-methylphenol), 1,1-bis(3,5-di-tert-butyl-2-hydroxyphenyl) ethane, and 2,2'-methylene bis(6-cyclohexyl-4-methylphenol)), which bound with a high affinity to CYP2C19 in silico. They exerted a profound cytotoxicity in vitro and interacted with several metabolic pathways, of which the 'cholesterol biosynthesis process' was the most affected. In addition, other affected pathways involved mitosis, DNA replication, and inflammation, suggesting an increase in hepatotoxicity. These results indicate that plastic-related compounds could damage the liver by affecting several molecular pathways.
- Date of acceptance
- 2023
- Autoren
- Matteo Rosellini
- Alicia Schulze
- Ejlal A Omer
- Nadeen T Ali
- Federico Marini
- Jan-Heiner Küpper
- Thomas Efferth
- Autoren-URL
- https://www.ncbi.nlm.nih.gov/pubmed/37630204
- DOI
- 10.3390/molecules28165952
- eISSN
- 1420-3049
- Externe Identifier
- PubMed Central ID: PMC10459118
- Funding acknowledgements
- Deutsche Forschungsgemeinschaft: GRK 2015/2
- Ausgabe der Veröffentlichung
- 16
- Zeitschrift
- Molecules
- Schlüsselwörter
- RNA sequencing
- cytotoxicity
- ecotoxicity
- hepatotoxicity
- microplastic
- Female
- Pregnancy
- Humans
- Plastics
- Hep G2 Cells
- Cytochrome P-450 CYP2C19
- Molecular Docking Simulation
- Transcriptome
- Sprache
- eng
- Country
- Switzerland
- PII
- molecules28165952
- Datum der Veröffentlichung
- 2023
- Status
- Published online
- Datum, an dem der Datensatz öffentlich gemacht wurde
- 2023
- Titel
- The Effect of Plastic-Related Compounds on Transcriptome-Wide Gene Expression on CYP2C19-Overexpressing HepG2 Cells.
- Sub types
- Journal Article
- Ausgabe der Zeitschrift
- 28
Data source: PubMed
- Beziehungen:
- Property of