The presence and inducibility of specific CYPs (1A1, 1A2, 1B1, 2B22, 3A22, 3A29 and 3A46) and the related transcriptional factors (AhR, CAR, PXR, and HNF4) were investigated, at activity and/or transcriptional level, in liver, respiratory and olfactory mucosa of control and b-naphthoflavone (bNF)-treated pigs an agonist of AhR, or rifampicin (RIF), an agonist of PXR. Experiments with real-time PCR showed that CYP1A1 mRNA was enhanced by bNF, although at different extent, in liver, respiratory and olfactory tissues, whereas mRNAs of CYP1A2 and 1B1 were increased only in liver. Accordingly, in microsomes of both nasal tissues, the transcriptional activation of CYP1A1 was accompanied by an induction of ethoxyresorufin deethylase activity (a marker of this isoform) but not of methoxyresorufin demethylase activity (a marker of CYP1A2). The rifampicin treatment resulted in a transcriptional activation of CYP2B22 and CYP3As genes in liver but not in respiratory and olfactory mucosa. In parallel, the marker activity of CYP2B (ethoxy 4-(trifluoromethyl)coumarin deethylase) and CYP3As (6b-testosterone hydroxylase and benzyloxyquinoline debenzylase) were induced in liver microsomes but not in the nasal ones. Considering thetranscriptional factors, the basal expression of AhR mRNAwas found to be as high in liver as in both nasaltissues but not susceptible to induction by _NF. Also PXR mRNA was found, aside liver, well expressed in the nasal tissues, whereas CAR and HNF4_ mRNAs were barely detected. In any case, these transcripts appeared to be enhanced by RIF treatment. Our results demonstrated that in the respiratory and olfactory mucosa of pig, although the presence of AhR, only CYP1A1, but not 1A2 and 1B1 resulted to be inducible by bNF. Similarly, itwas observed that in these nasal tissues, although the presence of PXR, neither CYP2B22 nor any CYP3A resulted to be inducible by RIF. Thus, the regulation mechanism of CYP1A2, 1B1, 2B22,3A22, 3A29, and 3A46, in the nasal mucosa involves tissue-enriched transcriptional factors others than AhR, CAR, PXR, and HNF4_, which are fundamental in liver.
Expression and inducibility of CYP1A1, 1A2, 1B1 by b naphthoflavone and CYP2B22, 3A22, 3A29, 3A46 by rifampicin in the respiratory and olfactory mucosa of pig.
Longo V;
2009
Abstract
The presence and inducibility of specific CYPs (1A1, 1A2, 1B1, 2B22, 3A22, 3A29 and 3A46) and the related transcriptional factors (AhR, CAR, PXR, and HNF4) were investigated, at activity and/or transcriptional level, in liver, respiratory and olfactory mucosa of control and b-naphthoflavone (bNF)-treated pigs an agonist of AhR, or rifampicin (RIF), an agonist of PXR. Experiments with real-time PCR showed that CYP1A1 mRNA was enhanced by bNF, although at different extent, in liver, respiratory and olfactory tissues, whereas mRNAs of CYP1A2 and 1B1 were increased only in liver. Accordingly, in microsomes of both nasal tissues, the transcriptional activation of CYP1A1 was accompanied by an induction of ethoxyresorufin deethylase activity (a marker of this isoform) but not of methoxyresorufin demethylase activity (a marker of CYP1A2). The rifampicin treatment resulted in a transcriptional activation of CYP2B22 and CYP3As genes in liver but not in respiratory and olfactory mucosa. In parallel, the marker activity of CYP2B (ethoxy 4-(trifluoromethyl)coumarin deethylase) and CYP3As (6b-testosterone hydroxylase and benzyloxyquinoline debenzylase) were induced in liver microsomes but not in the nasal ones. Considering thetranscriptional factors, the basal expression of AhR mRNAwas found to be as high in liver as in both nasaltissues but not susceptible to induction by _NF. Also PXR mRNA was found, aside liver, well expressed in the nasal tissues, whereas CAR and HNF4_ mRNAs were barely detected. In any case, these transcripts appeared to be enhanced by RIF treatment. Our results demonstrated that in the respiratory and olfactory mucosa of pig, although the presence of AhR, only CYP1A1, but not 1A2 and 1B1 resulted to be inducible by bNF. Similarly, itwas observed that in these nasal tissues, although the presence of PXR, neither CYP2B22 nor any CYP3A resulted to be inducible by RIF. Thus, the regulation mechanism of CYP1A2, 1B1, 2B22,3A22, 3A29, and 3A46, in the nasal mucosa involves tissue-enriched transcriptional factors others than AhR, CAR, PXR, and HNF4_, which are fundamental in liver.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
