Next Article in Journal
Pregnancy-Induced High Plasma Levels of Soluble Endoglin in Mice Lead to Preeclampsia Symptoms and Placental Abnormalities
Next Article in Special Issue
Recent Highlights of Research on miRNAs as Early Potential Biomarkers for Cardiovascular Complications of Type 2 Diabetes Mellitus
Previous Article in Journal
The Interfacial Interactions of Glycine and Short Glycine Peptides in Model Membrane Systems
Article

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

1
University Medical Center Groningen, Department of Pathology and Medical Biology, University of Groningen, 9713 GZ Groningen, The Netherlands
2
GRIAC Research Institute, University of Groningen, 9713 AV Groningen, The Netherlands
3
Department of Pulmonology and Allergology, Mongolian National University of Medical Sciences, Ulaanbaatar 14210, Mongolia
4
Faculty of Science and Engineering, University of Groningen, 9713 GZ Groningen, The Netherlands
5
Department of Pharmacokinetics, Toxicology and Targeting, Groningen Research Institute of Pharmacy, University of Groningen, 9713 AV Groningen, The Netherlands
6
University Medical Center Groningen, Department of Obstetrics and Gynecology, University of Groningen, 9713 GZ Groningen, The Netherlands
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2021, 22(1), 164; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22010164
Received: 20 November 2020 / Revised: 22 December 2020 / Accepted: 23 December 2020 / Published: 26 December 2020
(This article belongs to the Special Issue Epigenetics, Exosomes, and MicroRNAs in Metabolic Disorders)
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. View Full-Text
Keywords: epigenetics; CYP2A5; sex-difference; nicotine addiction; postnatal smoke exposure epigenetics; CYP2A5; sex-difference; nicotine addiction; postnatal smoke exposure
Show Figures

Figure 1

MDPI and ACS Style

Lkhagvadorj, K.; Zeng, Z.; Meyer, K.F.; Verweij, L.P.; Kooistra, W.; Reinders-Luinge, M.; Dijkhuizen, H.W.; de Graaf, I.A.M.; Plösch, T.; Hylkema, M.N. Postnatal Smoke Exposure Further Increases the Hepatic Nicotine Metabolism in Prenatally Smoke Exposed Male Offspring and Is Linked with Aberrant Cyp2a5 Methylation. Int. J. Mol. Sci. 2021, 22, 164. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22010164

AMA Style

Lkhagvadorj K, Zeng Z, Meyer KF, Verweij LP, Kooistra W, Reinders-Luinge M, Dijkhuizen HW, de Graaf IAM, Plösch T, Hylkema MN. Postnatal Smoke Exposure Further Increases the Hepatic Nicotine Metabolism in Prenatally Smoke Exposed Male Offspring and Is Linked with Aberrant Cyp2a5 Methylation. International Journal of Molecular Sciences. 2021; 22(1):164. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22010164

Chicago/Turabian Style

Lkhagvadorj, Khosbayar, Zhijun Zeng, Karolin F. Meyer, Laura P. Verweij, Wierd Kooistra, Marjan Reinders-Luinge, Henk W. Dijkhuizen, Inge A.M. de Graaf, Torsten Plösch, and Machteld N. Hylkema 2021. "Postnatal Smoke Exposure Further Increases the Hepatic Nicotine Metabolism in Prenatally Smoke Exposed Male Offspring and Is Linked with Aberrant Cyp2a5 Methylation" International Journal of Molecular Sciences 22, no. 1: 164. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22010164

Find Other Styles
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop