Modulation of CYP1A1 by PKC Inhibitors and TPA Pre-Treatments in MH1C1 Rat Hepatoma Cells Exposed to 3 -Methylcholanthrene

De Pascale, C., Domenicotti, C., Nitti, M., Marengo, B., Catalano, M., Scanarotti, C., Sanguineti, R., Siri, M., Ledda, S., Penco, S. and Bassi, A. 2009. Modulation of CYP1A1 by PKC Inhibitors and TPA Pre-Treatments in MH1C1 Rat Hepatoma Cells Exposed to 3 -Methylcholanthrene. The Open Toxicology Journal . (3), pp. 47-57. doi:10.2174/1874340400903010047

TitleModulation of CYP1A1 by PKC Inhibitors and TPA Pre-Treatments in MH1C1 Rat Hepatoma Cells Exposed to 3 -Methylcholanthrene
AuthorsDe Pascale, C., Domenicotti, C., Nitti, M., Marengo, B., Catalano, M., Scanarotti, C., Sanguineti, R., Siri, M., Ledda, S., Penco, S. and Bassi, A.
Abstract

Cytochrome P4501A1 (CYP1A1), an enzyme known to metabolize polycyclic aromatic hydrocarbons, is regulated by the aryl hydrocarbon receptor (AhR). The involvement of protein kinase C (PKC) in the regulation of AhR signal transduction pathway, has been widely studied but the role of specific PKC isoform(s) involved in this process it is not well clarified. To study which PKC isoform(s) is implicated in the regulation of CYP1A1, in the poorly tumorigenic MH1C1 rat hepatoma cells, we examined the effects of some PKC pharmacological inhibitors, Calphostin C (CAL), Staurosporine (STA) and H7, and of 12-0-tetradecanoyl phorbol 13-acetate (TPA), a PKC activator, on basal and 3- methylcholanthrene (MC)-induced CYP1A1 protein expression and mediated ethoxyresorufin O-deethylation (EROD) activity. In parallel, the activities of PKC-α, -βI, -δ and -ε isoforms, the most expressed in MH1C1 cells, were monitored. After pre-treatment with CAL, STA and H7, the MC-induced CYP1A1 protein and EROD activity were rapidly reduced with temporal profile similar to the profile of the activity of α and β1 PKC isoforms. Moreover, TPA pre-treatment induced a biphasic effect on EROD activity, and a decline of PKC -βI and -α, in first instance, and -δ and -ε activities later on. These findings clearly show that, in MH1C1 cells, PKC is involved in CYP1A1 regulation and that α and βI classic PKC isoforms play an active role in modulating this process.

KeywordsCYP1A1, PKC, TPA, PKC inhibitors, rat hepatoma cell line, in vitro.
JournalThe Open Toxicology Journal
Journal citation(3), pp. 47-57
ISSN1874-3404
Year2009
PublisherBentham Open
Publisher's versionTOTOXIJ-3-47.pdf
Digital Object Identifier (DOI)doi:10.2174/1874340400903010047
Publication dates
Published online02 Oct 2009
LicenseCC BY 4.0

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