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Degradation of pristine and oxidized single wall carbon nanotubes by CYP3A4
Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
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Number of Authors: 82019 (English)In: Biochemical and Biophysical Research Communications - BBRC, ISSN 0006-291X, E-ISSN 1090-2104, Vol. 515, no 3, p. 487-492Article in journal (Refereed) Published
Abstract [en]

Carbon nanotubes (CNTs) are a class of carbon based nanomaterials which have attracted substantial attention in recent years as they exhibit outstanding physical, mechanical and optical properties. In the last decade many studies have emerged of the underlying mechanisms behind CNT toxicity including malignant transformation, the formation of granulomas, inflammatory responses, oxidative stress, DNA damage and mutation. In the present investigation, we studied the biodegradation of single-walled carbon nanotubes (SWCNTs) by Cytochrome P450 enzymes (CYP3A4) through using Raman spectroscopy. CYP3A4 is known isozyme accountable for metabolizing various endogenous and exogenous xenobiotics. CYP3A4 is expressed dominantly in the liver and other organs including the lungs. Our results suggest that CYP3A4 has a higher affinity for p-SWNTs compared to c-SWNTs. HEK293 cellular viability was not compromised when incubated with SWNT. However, CYP3A4 transfected HEK293 cell line showed no digestion of cSWNTs after incubation for 96 h. Cellular uptake of c-SWNTs was observed by electron microscopy and localization of c-SWNTs was confirmed in endosomal vesicles and in the cytoplasm. This is the first study CYP3A4 degrading both p-SWNTs and c-SWNTs in an in vitro setup. Interestingly, our results show that CYP3A4 is more proficient in degrading p-SWNTs than c-SWNTs. We also employed computational modeling and docking assessments to develop a further understanding of the molecular interaction mechanism.

Place, publisher, year, edition, pages
2019. Vol. 515, no 3, p. 487-492
Keywords [en]
CYP 3A4, Carbon nanotubes, Biodegradation, Raman, CYP450
National Category
Biochemistry and Molecular Biology Biophysics
Identifiers
URN: urn:nbn:se:su:diva-170767DOI: 10.1016/j.bbrc.2019.05.097ISI: 000472986400014PubMedID: 31164198OAI: oai:DiVA.org:su-170767DiVA, id: diva2:1338732
Available from: 2019-07-24 Created: 2019-07-24 Last updated: 2019-07-24Bibliographically approved

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