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Prenatal nicotine exposure leads to decreased histone H3 lysine 9 (H3K9) methylation and increased p66shc expression in the neonatal pancreas

Published online by Cambridge University Press:  28 May 2021

Sergio Raez-Villanueva ,
Amrita Debnath ,
Daniel B. Hardy  and
Alison C. Holloway Open the ORCID record for Alison C. Holloway [Opens in a new window]
Sergio Raez-Villanueva
Affiliation:
Department of Obstetrics and Gynecology, McMaster University, Hamilton, ON, Canada
Amrita Debnath
Affiliation:
Department of Obstetrics and Gynecology, McMaster University, Hamilton, ON, Canada
Daniel B. Hardy
Affiliation:
Departments of Obstetrics and Gynecology and Physiology and Pharmacology, The Children’s Health Research Institute, The Lawson Health Research Institute, Western University, London, ON, Canada
Alison C. Holloway*
Affiliation:
Department of Obstetrics and Gynecology, McMaster University, Hamilton, ON, Canada
*
Address for correspondence: Dr. Alison Holloway, Department of Obstetrics & Gynecology, McMaster University, RM HSC-3N52, 1280 Main Street West, Hamilton, ON, Canada. Email: [email protected]
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Abstract

Prenatal exposure to nicotine, tobacco’s major addictive constituent, has been shown to reduce birth weight and increases apoptosis, oxidative stress, and mitochondrial dysfunction in the postnatal pancreas. Given that upregulated levels of the pro-oxidative adapter protein p66shc is observed in growth-restricted offspring and is linked to beta-cell apoptosis, the goal of this study was to investigate whether alterations in p66shc expression underlie the pancreatic deficits in nicotine-exposed offspring. Maternal administration of nicotine in rats increased p66shc expression in the neonatal pancreas. Similarly, nicotine treatment augmented p66shc expression in INS-1E pancreatic beta cells. Increased p66shc expression was also associated with decreased histone H3 lysine 9 methylation. Finally, nicotine increased the expression of Kdm4c, a key histone lysine demethylase, and decreased Suv39h1, a critical histone lysine methyltransferase. Collectively, these results suggest that upregulation of p66shc through posttranslational histone modifications may underlie the reported adverse outcomes of nicotine exposure on pancreatic function.

Keywords

Epigeneticshistone methylationnicotinep66Shcpancreatic beta cell
Type
Brief Reports
Information
Journal of Developmental Origins of Health and Disease , Volume 13 , Issue 2 , April 2022 , pp. 156 - 160
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Copyright
© The Author(s), 2021. Published by Cambridge University Press in association with International Society for Developmental Origins of Health and Disease

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