Expression of CYP2A3 mRNA and its regulation by 3-methylcholanthrene, pyrazole, and ß-ionone in rat tissues

Ferreira, Anna Beatriz Robottom; Aquino, S.R.; Queiroga, R.; Albano, Rodolpho Mattos; Pinto, Luís Felipe Ribeiro

doi:10.1590/s0100-879x2003000700003

Cited by 24 publications

(8 citation statements)

References 22 publications

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“…In OM, we detected the mRNA coding for CYP1A1, 1A2, 2A3, 2E1, 2G1, 2J4, and 4B, the expression of which had already been described by others at the protein level (Chen et al, 1992;Zhang et al, 1997;Wardlaw et al, 1998;Deshpande et al, 1999;Genter et al, 2002) or at the mRNA level (Nef et al, 1989;Zhang et al, 1997;Longo et al, 2000;Wang et al, 2002;Robottom-Ferreira et al, 2003). In addition, we identified for the first time the mRNA coding for CYP2A1, 2B2, 2B21, 2D1, 2D4, and 3A9.…”

Section: Downloaded Fromsupporting

confidence: 56%

“…Some studies specifically concern the formation of toxic metabolites by OM after the administration of various molecules and thus the potential role of P450 in nasal toxic events Gu et al, 1998;Longo et al, 2000). Recent papers focus on the possible induction of olfactory isoforms (Genter et al, 2002;Robottom-Ferreira et al, 2003). Only a few authors report a comparison between P450 activities or expression in OM and the liver.…”

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confidence: 99%

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Characterization of Microsomal Cytochrome P450-Dependent Monooxygenases in the Rat Olfactory Mucosa

Minn¹,

Pelczar²,

Denizot³

et al. 2005

Drug Metab Dispos

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ABSTRACT:Nasal administration of a drug ensures therapeutic action by rapid systemic absorption and/or the entry of some molecules into the brain through different routes. Many recent studies have pointed out the presence of xenobiotic-metabolizing enzymes in rat olfactory mucosa (OM). Nevertheless, very little is known about the precise identity of isoforms of cytochrome P450 (P450)-dependent monooxygenases (P450) and their metabolic function in this tissue. Therefore, we evaluated mRNA expression of 19 P450 isoforms by semiquantitative reverse transcriptase-polymerase chain reaction and measured their microsomal activity toward six model substrates. For purposes of comparison, studies were conducted on OM and the liver. Specific activities toward phenacetin, chlorzoxazone, and dextromethorphan are higher in OM than in the liver; those toward lauric acid and testosterone are similar in both tissues, and that toward tolbutamide is much lower in OM. There are considerable differences between the two tissues with regard to mRNA expression of P450 isoforms. Some isoforms are expressed in OM but not in the liver (CYP1A1, 2G1, 2B21, and 4B1), whereas mRNA of others (CYP2C6, 2C11, 2D2, 3A1, 3A2, and 4A1) is present only in hepatic tissue. Although expression of CYP1A2, 2A1, 2A3, 2B2, 2D1, 2D4, 2E1, 2J4, and 3A9 is noticed in both tissues, there are a number of quantitative differences. On the whole, our results strongly suggest that CYP1A1, 1A2, 2A3, 2E1, 2G1, and 3A9 are among the main functional isoforms present in OM, at least regarding activities toward the six tested substrates. The implication of olfactory P450-dependent monooxygenases in toxicology, pharmacology, and physiology should be further investigated.

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confidence: 56%

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confidence: 99%

Characterization of Microsomal Cytochrome P450-Dependent Monooxygenases in the Rat Olfactory Mucosa

Minn¹,

Pelczar²,

Denizot³

et al. 2005

Drug Metab Dispos

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“…We confirmed the upregulation of Metallothionein (Mt) 1 and 2 genes, which encode small cysteine rich proteins that bind metals such as zinc and copper and acts as antioxidants 34 and of Slc30a2 , which encodes a zinc transporter 34 by RT-PCR analysis ( Fig 2B ). RT-PCR analysis also confirmed the downregulation of Cyp2a3 (Cyp2a6 in humans and Cyp2a5 in mice), which is a cytochrome P450 isoform responsible for the activation of nitrosamines 35 36 . To investigate these gene expression changes in a more physiologically relevant ex vivo system, cultured primary rat hepatocytes were also incubated with control-CM and EPS-CM.…”

Section: Resultsmentioning

confidence: 73%

Electric Pulse Stimulation of Myotubes as an In Vitro Exercise Model: Cell-Mediated and Non-Cell-Mediated Effects

Gogh¹,

Alex

Stienstra

et al. 2015

Sci Rep

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Regular exercise has emerged as one of the best therapeutic strategies to prevent and treat type-2-diabetes. Exercise-induced changes in the muscle secretome, consisting of myokines and metabolites, may underlie the inter-organ communication between muscle and other organs. To investigate this crosstalk, we developed an in vitro system in which mouse C2C12 myotubes underwent electric pulse stimulation (EPS) to induce contraction. Subsequently the effects of EPS-conditioned media (EPS-CM) on hepatocytes were investigated. Here, we demonstrate that EPS-CM induces Metallothionein 1/2 and Slc30a2 gene expression and reduces Cyp2a3 gene expression in rat hepatocytes. When testing EPS-CM that was generated in the absence of C2C12 myotubes (non-cell EPS-CM) no decrease in Cyp2a3 expression was detected. However, similar inductions in hepatic Mt1/2 and Slc30a2 expression were observed. Non-cell EPS-CM were also applied to C2C12 myotubes and compared to C2C12 myotubes that underwent EPS: here changes in AMPK phosphorylation and myokine secretion largely depended on EPS-induced contraction. Taken together, these findings indicate that EPS can alter C2C12 myotube function and thereby affect gene expression in cells subjected to EPS-CM (Cyp2a3). However, EPS can also generate non-cell-mediated changes in cell culture media, which can affect gene expression in cells subjected to EPS-CM too. While EPS clearly represents a valuable tool in exercise research, care should be taken in experimental design to control for non-cell-mediated effects.

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“…Similarly, pyridine has been shown to induce 1A1 (Iba et al, 2002) and 2B1/2B2 (Kim et al, 1993), as well as CYP2E1. Pyrazole has been reported to induce 2C, 2E, and 2J, along with other isoforms (Park et al, 1993;Robottom-Ferreira et al, 2003). Ethanol has been shown to induce CYP2E1 and 3A4 (Sinclair et al, 1998).…”

Section: Poloyac Et Almentioning

confidence: 99%

The Effect of Isoniazid on Cyp2e1- And Cyp4a-Mediated Hydroxylation of Arachidonic Acid in the Rat Liver and Kidney

Poloyac¹,

Tortorici²,

Przychodzin³

et al. 2004

Drug Metab Dispos

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ABSTRACT:Cytochrome P450 (P450) bioactivation of arachidonic acid to hydroxyeicosatetraenoic acids (HETEs) has been reported to be isoform-and tissue-specific. To determine whether altered P450 expression affects the production of these metabolites, the formation of HETEs after isoniazid-mediated CYP2E1 induction was evaluated in the rat liver and kidney. Male Sprague-Dawley rats received isoniazid (200 mg/kg) or saline intraperitoneally once daily for 5 days. Chlorzoxazone, lauric acid, and arachidonic acid hydroxylation was measured in liver and kidney microsomes with and without preincubation with the specific CYP2E1 inhibitor, trans-1,2-dichloroethylene (DCE). P450 isoform content and tissue HETE metabolite concentrations were also determined. Isoniazid increased CYP2E1 protein, and the 6-hydroxychlorzoxazone formation rate was increased by 2.7 ؎ 0.3-and 2.2 ؎ 0.5-fold in liver and kidney, respectively. Formation of 19-HETE and 11-hydroxylauric acid was induced 2.3 ؎ 0.6-fold and 2.2 ؎ 0.4-fold in the liver, respectively, with no difference in the kidney. All of the induced activities were attenuated by DCE. An unanticipated decrease in liver CYP4A expression and in vitro 20-HETE formation rate was observed after isoniazid administration. Isoniazid decreased liver and kidney 20-HETE content to 34 ؎ 10% and 15.6 ؎ 5.3% of control, respectively, without significantly altering tissue 19-HETE concentration. Based on these findings, we conclude that under induced conditions, CYP2E1 is a primary enzyme involved in liver, but not kidney, formation of 19-HETE. In addition, formation of both CYP4A and 20-HETE is reduced in the liver by isoniazid. It was also demonstrated that tissue concentrations parallel in vitro inhibited formation rates for 20-HETE, but not the induced 19-HETE formation in the liver.

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Expression of CYP2A3 mRNA and its regulation by 3-methylcholanthrene, pyrazole, and ß-ionone in rat tissues

Cited by 24 publications

References 22 publications

Characterization of Microsomal Cytochrome P450-Dependent Monooxygenases in the Rat Olfactory Mucosa

Characterization of Microsomal Cytochrome P450-Dependent Monooxygenases in the Rat Olfactory Mucosa

Electric Pulse Stimulation of Myotubes as an In Vitro Exercise Model: Cell-Mediated and Non-Cell-Mediated Effects

The Effect of Isoniazid on Cyp2e1- And Cyp4a-Mediated Hydroxylation of Arachidonic Acid in the Rat Liver and Kidney

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