دورية أكاديمية
Prenatal smoke exposure induces persistent Cyp2a5 methylation and increases nicotine metabolism in the liver of neonatal and adult male offspring
| العنوان: | Prenatal smoke exposure induces persistent Cyp2a5 methylation and increases nicotine metabolism in the liver of neonatal and adult male offspring |
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| المؤلفون: | Khosbayar Lkhagvadorj, Karolin F. Meyer, Laura P. Verweij, Wierd Kooistra, Marjan Reinders-Luinge, Henk W. Dijkhuizen, Inge A. M. de Graaf, Torsten Plösch, Machteld N. Hylkema |
| المصدر: | Epigenetics, Vol 15, Iss 12, Pp 1370-1385 (2020) |
| بيانات النشر: | Taylor & Francis Group, 2020. |
| سنة النشر: | 2020 |
| المجموعة: | LCC:Genetics |
| مصطلحات موضوعية: | prenatal smoke exposure, epigenetics, cotinine, cyp2a5, nicotine dependence, sex difference, mouse model, Genetics, QH426-470 |
| الوصف: | Prenatal smoke exposure (PSE) is a risk factor for nicotine dependence. One susceptibility gene for nicotine dependence is Cytochrome P450 (CYP) 2A6, an enzyme responsible for the conversion of nicotine to cotinine and nicotine clearance in the liver. Higher activity of the CYP2A6 enzyme is associated with nicotine dependence, but no research has addressed the PSE effects on the CYP2A6 gene or its mouse homologue Cyp2a5. We hypothesized that PSE affects Cyp2a5 promoter methylation, Cyp2a5 mRNA levels, and nicotine metabolism in offspring. We used a smoke-exposed pregnant mouse model. RNA, DNA, and microsomal protein were isolated from liver tissue of foetal, neonatal, and adult offspring. Enzyme activity, Cyp2a5 mRNA levels, and Cyp2a5 methylation status of six CpG sites within the promoter region were analysed via HPLC, RT-PCR, and bisulphite pyrosequencing. Our data show that PSE induced higher cotinine levels in livers of male neonatal and adult offspring compared to controls. PSE-induced cotinine levels in neonates correlated with Cyp2a5 mRNA expression and promoter methylation at CpG-7 and CpG+45. PSE increased methylation in almost all CpG sites in foetal offspring, and this effect persisted at CpG-74 in male neonatal and adult offspring. Our results indicate that male offspring of mothers which were exposed to cigarette smoke during pregnancy have a higher hepatic nicotine metabolism, which could be regulated by DNA methylation. Given the detected persistence into adulthood, extrapolation to the human situation suggests that sons born from smoking mothers could be more susceptible to nicotine dependence later in life. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 1559-2294 1559-2308 15592294 |
| العلاقة: | https://doaj.org/toc/1559-2294Test; https://doaj.org/toc/1559-2308Test |
| DOI: | 10.1080/15592294.2020.1782655 |
| الوصول الحر: | https://doaj.org/article/9c83266db7144cbbba7fce50a2335ecfTest |
| رقم الانضمام: | edsdoj.9c83266db7144cbbba7fce50a2335ecf |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 15592294 15592308 |
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| DOI: | 10.1080/15592294.2020.1782655 |