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Degradation of pristine and oxidized single wall carbon nanotubes by CYP3A4

Journal article
Authors R. El-Sayed
Ahmed Waraky
K. Ezzat
R. Albabtain
K. ElGammal
S. Shityakov
M. Muhammed
M. Hassan
Published in Biochemical and Biophysical Research Communications
Volume 515
Issue 3
Pages 487-492
ISSN 0006-291X
Publication year 2019
Published at Institute of Biomedicine
Pages 487-492
Language en
Links dx.doi.org/10.1016/j.bbrc.2019.05.0...
Keywords Biodegradation, Carbon nanotubes, CYP 3A4, CYP450, Raman, cytochrome P450 3A4, single walled nanotube, Article, cell transport, cell viability, cytoplasm, electron microscopy, endosome, enzyme metabolism, HEK293 cell line, human, human cell, in vitro study, incubation time, liver, liver metabolism, lung function, mathematical model, molecular docking, molecular interaction, oxidation, priority journal, protein degradation, protein expression, Raman spectrometry
Subject categories Medical Biotechnology

Abstract

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 c-SWNTs 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. © 2019 Elsevier Inc.

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