Prenatal nicotine exposure leads to decreased histone H3 lysine 9 (H3K9) methylation and increased p66shc expression in the neonatal pancreas. (28th April 2022)

• Record Type: Journal Article
• Authors: Raez-Villanueva, Sergio; Debnath, Amrita; Hardy, Daniel B.; Holloway, Alison C.
• Is Part Of: Journal of developmental origins of health and disease. Volume 13:Number 2(2022)
• Page Start: 156
• Page End: 160
• Publication Date: 2022-04-28
• Subjects: Epigenetics -- histone methylation -- nicotine -- p66Shc -- pancreatic beta cell; Developmental biology -- Periodicals; Embryology, Human -- Periodicals; Disease susceptibility -- Periodicals; Prenatal influences -- Periodicals; Diseases -- Causes and theories of causation -- Periodicals; 612.64
• DOI: 10.1017/S2040174421000283
• Languages: English
• ISSNs: 2040-1744

Abstract

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.