Cell type-specific expression and localization of cytochrome P450 isoforms in tridimensional aggregating rat brain cell cultures.

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State: Public
Version: Final published version
Serval ID
serval:BIB_A6C4F3AA22F9
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Cell type-specific expression and localization of cytochrome P450 isoforms in tridimensional aggregating rat brain cell cultures.
Journal
Toxicology In Vitro : An International Journal Published In Association With Bibra
Author(s)
Vichi S., Sandström von Tobel J., Gemma S., Stanzel S., Kopp-Schneider A., Monnet-Tschudi F., Testai E., Zurich M.G.
ISSN
1879-3177 (Electronic)
ISSN-L
0887-2333
Publication state
Published
Issued date
2015
Peer-reviewed
Oui
Volume
30
Number
1 Pt A
Pages
176-184
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Abstract
Within the Predict-IV FP7 project a strategy for measurement of in vitro biokinetics was developed, requiring the characterization of the cellular model used, especially regarding biotransformation, which frequently depends on cytochrome P450 (CYP) activity. The extrahepatic in situ CYP-mediated metabolism is especially relevant in target organ toxicity. In this study, the constitutive mRNA levels and protein localization of different CYP isoforms were investigated in 3D aggregating brain cell cultures. CYP1A1, CYP2B1/B2, CYP2D2/4, CYP2E1 and CYP3A were expressed; CYP1A1 and 2B1 represented almost 80% of the total mRNA content. Double-immunolabeling revealed their presence in astrocytes, in neurons, and to a minor extent in oligodendrocytes, confirming the cell-specific localization of CYPs in the brain. These results together with the recently reported formation of an amiodarone metabolite following repeated exposure suggest that this cell culture system possesses some metabolic potential, most likely contributing to its high performance in neurotoxicological studies and support the use of this model in studying brain neurotoxicity involving mechanisms of toxication/detoxication.
Keywords
Aging, Animals, Brain/cytology, Cells, Cultured, Cytochrome P-450 Enzyme System/classification, Cytochrome P-450 Enzyme System/metabolism, Embryo, Mammalian/cytology, Gene Expression Regulation, Enzymologic, Hepatocytes, Isoenzymes, Neurons/metabolism, Protein Transport, Rats
Pubmed
Web of science
Open Access
Yes
Create date
07/12/2015 13:07
Last modification date
20/08/2019 15:11
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