Expression and inducibility of CYP1A1, 1A2, 1B1 by β-naphthoflavone and CYP2B22, CYP3As by rifampicin in heart regions and coronary arteries of pig.
In this study, the constitutive and inducible expression of the CYP genes (1A1, 1A2, 1B1, 2B22, 3A22, 3A29 and 3A46), related transcriptional factors (AhR, CAR, PXR, and Nrf2) and the antioxidant enzymes SOD, catalase, GSSH-reductase and GSH-peroxidase were investigated in the liver, heart regions and coronary arteries of control pigs and pigs treated with β-naphthoflavone (βNF) or with rifampicin (RIF). Real-time PCR experiments and enzymatic or immunoblot assays showed that CYP1A1 was predominantly enhanced by βNF in a similar manner in all the heart regions, whereas antioxidant enzyme activity was not affected. The rifampicin treatment resulted in an induction of CYP2B22 and CYP3As, at the transcriptional, activity and protein level in liver but not in heart nor in the coronary arteries, despite the expression of CAR and PXR in the cardiac tissues. These results obtained in vivo suggest that pig cardiac tissues may represent a useful model for humans.
Istituto di Fisiologia Clinica CNR, Area della Ricerca CNR, via Moruzzi, 1, 56100 Pisa, Italy.
Andrea
A
Messina
Emanuela
E
Puccinelli
Pier Giovanni
PG
Gervasi
Vincenzo
V
Longo
D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases / Q000096:biosynthesis*; D002374:Catalase / Q000096:biosynthesis; D003331:Coronary Vessels / Q000187:drug effects* / Q000378:metabolism; D019363:Cytochrome P-450 CYP1A1 / Q000096:biosynthesis*; D019388:Cytochrome P-450 CYP1A2 / Q000096:biosynthesis*; D065633:Cytochrome P-450 CYP1B1; D051544:Cytochrome P-450 CYP3A / Q000096:biosynthesis*; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis*; D004790:Enzyme Induction / Q000187:drug effects; D006321:Heart / Q000187:drug effects*; D009206:Myocardium / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction / Q000662:veterinary; D012293:Rifampin / Q000494:pharmacology*; D013482:Superoxide Dismutase / Q000096:biosynthesis; D013552:Swine / Q000378:metabolism; D019324:beta-Naphthoflavone / Q000494:pharmacology*
D019324:beta-Naphthoflavone; D003577:Cytochrome P-450 Enzyme System; D002374:Catalase; D001189:Aryl Hydrocarbon Hydroxylases; C585496:CYP1B1 protein, human; D019363:Cytochrome P-450 CYP1A1; D019388:Cytochrome P-450 CYP1A2; D065633:Cytochrome P-450 CYP1B1; D051544:Cytochrome P-450 CYP3A; D013482:Superoxide Dismutase; D012293:Rifampin