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

Toxicology in Vitro : an International Journal Published in Association with BIBRA
S VichiMarie-Gabrielle Zurich

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.

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Citations

Sep 13, 2015·Toxicology in Vitro : an International Journal Published in Association with BIBRA·Nynke I KramerEmanuela Testai
Feb 11, 2015·Toxicology in Vitro : an International Journal Published in Association with BIBRA·Giuliana PomponioEmanuela Testai

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