title: Effects of 4-nonylphenol on hepatic gene expression of peroxisome proliferator-activated receptors and cytochrome P450 isoforms (CYP1A1 and CYP3A4) in juvenile sole (Solea solea).
abstract: The objective of the present study was to investigate the modulatory effects of the xenoestrogen 4-nonylphenol (4-NP) on hepatic peroxisome proliferator-activated receptor (PPAR) α and β gene expression patterns in relation to the detoxification pathways mediated by cytochrome P450 isoforms (CYP1A1 and CYP3A4). Waterborne 4-NP-induced effects were compared with those of 10(-8)M 17β-estradiol (E2) by using in vivo dose-response experiments carried out with juvenile sole (Solea solea). Compared to the controls, significantly higher levels of PPARα mRNAs were found in fish treated with E2 or 4-NP (10(-6)M) 3 d after exposure; the highest dose of 4-NP also caused up-regulation of retinoid X receptor α (RXRα) transcript levels. On the contrary, PPARβ gene expression was not modulated by E2 or 4-NP. Our data show that 4-NP-induced PPARα mRNA levels coincide with suppression of CYP1A1 and CYP3A4 expression similarly to E2. The results from these in vivo studies suggest the presence of cross-talk between nuclear receptor-mediated signaling pathways and PPARα that may result in modulation of CYP450 isoforms expression following 4-NP treatment in sole liver.
authors.affiliation: School of Biosciences and Biotechnologies, University of Camerino, Via Gentile III Da Varano, I-62032 Camerino, MC, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Cocci
authors.forename: Gilberto
authors.initials: G
authors.lastname: Mosconi
authors.forename: Francesco Alessandro
authors.initials: FA
authors.lastname: Palermo
mesh_terms: D000818:Animals; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics* / Q000378:metabolism; D051544:Cytochrome P-450 CYP3A / Q000235:genetics / Q000378:metabolism*; D005412:Flatfishes / Q000235:genetics* / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects*; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D047493:PPAR alpha / Q000235:genetics / Q000378:metabolism; D047492:Peroxisome Proliferator-Activated Receptors / Q000235:genetics* / Q000378:metabolism; D010636:Phenols / Q000633:toxicity*; D012333:RNA, Messenger / Q000378:metabolism; D014874:Water Pollutants, Chemical / Q000633:toxicity*
chemical_list: D047493:PPAR alpha; D047492:Peroxisome Proliferator-Activated Receptors; D010636:Phenols; D012333:RNA, Messenger; D014874:Water Pollutants, Chemical; D019363:Cytochrome P-450 CYP1A1; D051544:Cytochrome P-450 CYP3A; C041594:4-nonylphenol
keywords: 4-Nonylphenol; Cytochromes P450; Peroxisome proliferator-activated receptors; Solea solea