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Influence of Selected Carbon Nanostructures on the CYP2C9 Enzyme of the P450 Cytochrome

Carbon nanostructures have recently gained significant interest from scientists due to their unique physicochemical properties and low toxicity. They can accumulate in the liver, which is the main expression site of cytochrome P450 (CYP450) enzymes. These enzymes play an important role in the metabo...

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Autores principales: Sekretarska, Justyna, Szczepaniak, Jarosław, Sosnowska, Malwina, Grodzik, Marta, Kutwin, Marta, Wierzbicki, Mateusz, Jaworski, Sławomir, Bałaban, Jaśmina, Daniluk, Karolina, Sawosz, Ewa, Chwalibog, André, Strojny, Barbara
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6947289/
https://www.ncbi.nlm.nih.gov/pubmed/31835701
http://dx.doi.org/10.3390/ma12244149
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author Sekretarska, Justyna
Szczepaniak, Jarosław
Sosnowska, Malwina
Grodzik, Marta
Kutwin, Marta
Wierzbicki, Mateusz
Jaworski, Sławomir
Bałaban, Jaśmina
Daniluk, Karolina
Sawosz, Ewa
Chwalibog, André
Strojny, Barbara
author_facet Sekretarska, Justyna
Szczepaniak, Jarosław
Sosnowska, Malwina
Grodzik, Marta
Kutwin, Marta
Wierzbicki, Mateusz
Jaworski, Sławomir
Bałaban, Jaśmina
Daniluk, Karolina
Sawosz, Ewa
Chwalibog, André
Strojny, Barbara
author_sort Sekretarska, Justyna
collection PubMed
description Carbon nanostructures have recently gained significant interest from scientists due to their unique physicochemical properties and low toxicity. They can accumulate in the liver, which is the main expression site of cytochrome P450 (CYP450) enzymes. These enzymes play an important role in the metabolism of exogenous compounds, such as drugs and xenobiotics. Altered activity or expression of CYP450 enzymes may lead to adverse drug effects and toxicity. The objective of this study was to evaluate the influence of three carbon nanostructures on the activity and expression at the mRNA and protein levels of CYP2C9 isoenzyme from the CYP2C subfamily: Diamond nanoparticles, graphite nanoparticles, and graphene oxide platelets. The experiments were conducted using two in vitro models. A microsome model was used to assess the influence of the three-carbon nanostructures on the activity of the CYP2C9 isoenzyme. The CYP2C9 gene expression at the mRNA and protein levels was determined using a hepatoma-derived cell line HepG2. The experiments have shown that all examined nanostructures inhibit the enzymatic activity of the studied isoenzymes. Moreover, a decrease in the expression at the mRNA and protein levels was also observed. This indicates that despite low toxicity, the nanostructures can alter the enzymatic function of CYP450 enzymes, and the molecular pathways involved in their expression.
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spelling pubmed-69472892020-01-13 Influence of Selected Carbon Nanostructures on the CYP2C9 Enzyme of the P450 Cytochrome Sekretarska, Justyna Szczepaniak, Jarosław Sosnowska, Malwina Grodzik, Marta Kutwin, Marta Wierzbicki, Mateusz Jaworski, Sławomir Bałaban, Jaśmina Daniluk, Karolina Sawosz, Ewa Chwalibog, André Strojny, Barbara Materials (Basel) Article Carbon nanostructures have recently gained significant interest from scientists due to their unique physicochemical properties and low toxicity. They can accumulate in the liver, which is the main expression site of cytochrome P450 (CYP450) enzymes. These enzymes play an important role in the metabolism of exogenous compounds, such as drugs and xenobiotics. Altered activity or expression of CYP450 enzymes may lead to adverse drug effects and toxicity. The objective of this study was to evaluate the influence of three carbon nanostructures on the activity and expression at the mRNA and protein levels of CYP2C9 isoenzyme from the CYP2C subfamily: Diamond nanoparticles, graphite nanoparticles, and graphene oxide platelets. The experiments were conducted using two in vitro models. A microsome model was used to assess the influence of the three-carbon nanostructures on the activity of the CYP2C9 isoenzyme. The CYP2C9 gene expression at the mRNA and protein levels was determined using a hepatoma-derived cell line HepG2. The experiments have shown that all examined nanostructures inhibit the enzymatic activity of the studied isoenzymes. Moreover, a decrease in the expression at the mRNA and protein levels was also observed. This indicates that despite low toxicity, the nanostructures can alter the enzymatic function of CYP450 enzymes, and the molecular pathways involved in their expression. MDPI 2019-12-11 /pmc/articles/PMC6947289/ /pubmed/31835701 http://dx.doi.org/10.3390/ma12244149 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Sekretarska, Justyna
Szczepaniak, Jarosław
Sosnowska, Malwina
Grodzik, Marta
Kutwin, Marta
Wierzbicki, Mateusz
Jaworski, Sławomir
Bałaban, Jaśmina
Daniluk, Karolina
Sawosz, Ewa
Chwalibog, André
Strojny, Barbara
Influence of Selected Carbon Nanostructures on the CYP2C9 Enzyme of the P450 Cytochrome
title Influence of Selected Carbon Nanostructures on the CYP2C9 Enzyme of the P450 Cytochrome
title_full Influence of Selected Carbon Nanostructures on the CYP2C9 Enzyme of the P450 Cytochrome
title_fullStr Influence of Selected Carbon Nanostructures on the CYP2C9 Enzyme of the P450 Cytochrome
title_full_unstemmed Influence of Selected Carbon Nanostructures on the CYP2C9 Enzyme of the P450 Cytochrome
title_short Influence of Selected Carbon Nanostructures on the CYP2C9 Enzyme of the P450 Cytochrome
title_sort influence of selected carbon nanostructures on the cyp2c9 enzyme of the p450 cytochrome
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6947289/
https://www.ncbi.nlm.nih.gov/pubmed/31835701
http://dx.doi.org/10.3390/ma12244149
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