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Postnatal Smoke Exposure Further Increases the Hepatic Nicotine Metabolism in Prenatally Smoke Exposed Male Offspring and Is Linked with Aberrant Cyp2a5 Methylation

Prenatal smoke exposure (PreSE) is a risk factor for nicotine dependence, which is further enhanced by postnatal smoke exposure (PostSE). One susceptibility gene to nicotine dependence is Cytochrome P450 (CYP) 2A6, an enzyme responsible for the conversion of nicotine to cotinine in the liver. Higher...

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Autores principales: Lkhagvadorj, Khosbayar, Zeng, Zhijun, Meyer, Karolin F., Verweij, Laura P., Kooistra, Wierd, Reinders-Luinge, Marjan, Dijkhuizen, Henk W., de Graaf, Inge A. M., Plösch, Torsten, Hylkema, Machteld N.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7795156/
https://www.ncbi.nlm.nih.gov/pubmed/33375250
http://dx.doi.org/10.3390/ijms22010164
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author Lkhagvadorj, Khosbayar
Zeng, Zhijun
Meyer, Karolin F.
Verweij, Laura P.
Kooistra, Wierd
Reinders-Luinge, Marjan
Dijkhuizen, Henk W.
de Graaf, Inge A. M.
Plösch, Torsten
Hylkema, Machteld N.
author_facet Lkhagvadorj, Khosbayar
Zeng, Zhijun
Meyer, Karolin F.
Verweij, Laura P.
Kooistra, Wierd
Reinders-Luinge, Marjan
Dijkhuizen, Henk W.
de Graaf, Inge A. M.
Plösch, Torsten
Hylkema, Machteld N.
author_sort Lkhagvadorj, Khosbayar
collection PubMed
description Prenatal smoke exposure (PreSE) is a risk factor for nicotine dependence, which is further enhanced by postnatal smoke exposure (PostSE). One susceptibility gene to nicotine dependence is Cytochrome P450 (CYP) 2A6, an enzyme responsible for the conversion of nicotine to cotinine in the liver. Higher CYP2A6 activity is associated with nicotine dependence and could be regulated through DNA methylation. In this study we investigated whether PostSE further impaired PreSE-induced effects on nicotine metabolism, along with Cyp2a5, orthologue of CYP2A6, mRNA expression and DNA methylation. Using a mouse model where prenatally smoke-exposed adult offspring were exposed to cigarette smoke for 3 months, enzyme activity, mRNA levels, and promoter methylation of hepatic Cyp2a5 were evaluated. We found that in male offspring, PostSE increased PreSE-induced cotinine levels and Cyp2a5 mRNA expression. In addition, both PostSE and PreSE changed Cyp2a5 DNA methylation in male groups. PreSE however decreased cotinine levels whereas it had no effect on Cyp2a5 mRNA expression or methylation. These adverse outcomes of PreSE and PostSE were most prominent in males. When considered in the context of the human health aspects, the combined effect of prenatal and adolescent smoke exposure could lead to an accelerated risk for nicotine dependence later in life.
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spelling pubmed-77951562021-01-10 Postnatal Smoke Exposure Further Increases the Hepatic Nicotine Metabolism in Prenatally Smoke Exposed Male Offspring and Is Linked with Aberrant Cyp2a5 Methylation Lkhagvadorj, Khosbayar Zeng, Zhijun Meyer, Karolin F. Verweij, Laura P. Kooistra, Wierd Reinders-Luinge, Marjan Dijkhuizen, Henk W. de Graaf, Inge A. M. Plösch, Torsten Hylkema, Machteld N. Int J Mol Sci Article Prenatal smoke exposure (PreSE) is a risk factor for nicotine dependence, which is further enhanced by postnatal smoke exposure (PostSE). One susceptibility gene to nicotine dependence is Cytochrome P450 (CYP) 2A6, an enzyme responsible for the conversion of nicotine to cotinine in the liver. Higher CYP2A6 activity is associated with nicotine dependence and could be regulated through DNA methylation. In this study we investigated whether PostSE further impaired PreSE-induced effects on nicotine metabolism, along with Cyp2a5, orthologue of CYP2A6, mRNA expression and DNA methylation. Using a mouse model where prenatally smoke-exposed adult offspring were exposed to cigarette smoke for 3 months, enzyme activity, mRNA levels, and promoter methylation of hepatic Cyp2a5 were evaluated. We found that in male offspring, PostSE increased PreSE-induced cotinine levels and Cyp2a5 mRNA expression. In addition, both PostSE and PreSE changed Cyp2a5 DNA methylation in male groups. PreSE however decreased cotinine levels whereas it had no effect on Cyp2a5 mRNA expression or methylation. These adverse outcomes of PreSE and PostSE were most prominent in males. When considered in the context of the human health aspects, the combined effect of prenatal and adolescent smoke exposure could lead to an accelerated risk for nicotine dependence later in life. MDPI 2020-12-26 /pmc/articles/PMC7795156/ /pubmed/33375250 http://dx.doi.org/10.3390/ijms22010164 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Lkhagvadorj, Khosbayar
Zeng, Zhijun
Meyer, Karolin F.
Verweij, Laura P.
Kooistra, Wierd
Reinders-Luinge, Marjan
Dijkhuizen, Henk W.
de Graaf, Inge A. M.
Plösch, Torsten
Hylkema, Machteld N.
Postnatal Smoke Exposure Further Increases the Hepatic Nicotine Metabolism in Prenatally Smoke Exposed Male Offspring and Is Linked with Aberrant Cyp2a5 Methylation
title Postnatal Smoke Exposure Further Increases the Hepatic Nicotine Metabolism in Prenatally Smoke Exposed Male Offspring and Is Linked with Aberrant Cyp2a5 Methylation
title_full Postnatal Smoke Exposure Further Increases the Hepatic Nicotine Metabolism in Prenatally Smoke Exposed Male Offspring and Is Linked with Aberrant Cyp2a5 Methylation
title_fullStr Postnatal Smoke Exposure Further Increases the Hepatic Nicotine Metabolism in Prenatally Smoke Exposed Male Offspring and Is Linked with Aberrant Cyp2a5 Methylation
title_full_unstemmed Postnatal Smoke Exposure Further Increases the Hepatic Nicotine Metabolism in Prenatally Smoke Exposed Male Offspring and Is Linked with Aberrant Cyp2a5 Methylation
title_short Postnatal Smoke Exposure Further Increases the Hepatic Nicotine Metabolism in Prenatally Smoke Exposed Male Offspring and Is Linked with Aberrant Cyp2a5 Methylation
title_sort postnatal smoke exposure further increases the hepatic nicotine metabolism in prenatally smoke exposed male offspring and is linked with aberrant cyp2a5 methylation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7795156/
https://www.ncbi.nlm.nih.gov/pubmed/33375250
http://dx.doi.org/10.3390/ijms22010164
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