Expression of a novel cytochrome P450 4T gene in rare minnow (Gobiocypris rarus) following perfluorooctanoic acid exposure.

Cytochrome P450s play an important role in the biotransformation of endogenous substrates and xenobiotics; however, little is known about the function of the CYP4T subfamily in the transformation of environmental pollutants in fish. We isolated a full-length cDNA sequence (designated as CYP4T11) from rare minnow (Gobiocypris rarus) liver by rapid amplification of cDNA ends. The open reading frame encoded a 467-residue protein that exhibited 87% and 71% identity with zebrafish CYP4T8 and European sea bass CYP4T2, respectively. CYP4T11 was predominantly expressed in liver and intestine with lower expression in the gill and brain. To further examine the function of CYP4T11 in pollutant metabolism, the effects of perfluorooctanoic acid (PFOA) exposure on the transcriptional expression of CYP4T11 and two possible upstream regulators, peroxisome proliferator-activated receptor alpha (PPARalpha) and peroxisome proliferator-activated receptor gamma (PPARgamma), were determined in rare minnow gills and livers. PFOA induced a consistent significant upregulation of both PPARalpha and PPARgamma and a nonsignificant increase of CYP4T11 in the gill. In the liver, induced expression of PPARgamma was observed, although no obvious changes in PPARalpha expression were observed. Induction of CYP4T11 was only observed in males at the highest concentration of PFOA. These results suggest that the PPAR-CYP4T11 signaling pathway may be involved in PFOA-induced gill toxicity. Since the induced expression of CYP4T11 in liver was not consistent with the PPAR regulators, complex tissue-specific transcriptional regulation of CYP4T11 following PFOA exposure likely occurs.