Smoking and Promoter-Specific Deoxyribonucleic Acid Methylation of the Atrial Natriuretic Peptide Gene: Methylation of Smokers and Non-Smokers Differs Significantly during Withdrawal

Glahn, Alexander; Rhein, Mathias; Frieling, Helge; Schuster, Rilana; Aissami, Alain El; Bleich, Stefan; Hillemacher, Thomas; Muschler, Marc

doi:10.1159/000486279

Cited by 6 publications

(2 citation statements)

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“…However, endogenous peptide expression is also regulated by epigenetic mechanisms. For example, during withdrawal of both tobacco smoking and alcohol consumption, expression of natriuretic peptides and vasopressin are regulated by changing DNA methylation patterns in the promotor regions of the peptides [125–128]. HDACs are able to downregulate the expression of cationic antimicrobial peptides; therefore, treatment with HDACi can be an alternative approach to combat bacterial infections and tackle the problem of emerging antibiotic resistance by upregulating the expression of these antimicrobial peptides [129].…”

Section: Effects Of Epigenetics On Peptide Expressionmentioning

confidence: 99%

Peptides as epigenetic modulators: therapeutic implications

2019

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Peptides originating from different sources (endogenous, food derived, environmental, and synthetic) are able to influence different aspects of epigenetic regulation. Endogenous short peptides, resulting from proteolytic cleavage of proteins or upon translation of non-annotated out of frame transcripts, can block DNA methylation and hereby regulate gene expression. Peptides entering the body by digestion of food-related proteins can modulate DNA methylation and/or histone acetylation while environmental peptides, synthesized by bacteria, fungi, and marine sponges, mainly inhibit histone deacetylation. In addition, synthetic peptides that reverse or inhibit different epigenetic modifications of both histones and the DNA can be developed as well. Next to these DNA and histone modifications, peptides can also influence the expression of non-coding RNAs such as lncRNAs and the maturation of miRNAs. Seen the advantages over small molecules, the development of peptide therapeutics is an interesting approach to treat diseases with a strong epigenetic basis like cancer and Alzheimer’s disease. To date, only a limited number of drugs with a proven epigenetic mechanism of action have been approved by the FDA of which two (romidepsin and nesiritide) are peptides. A large knowledge gap concerning epigenetic effects of peptides is present, and this class of molecules deserves more attention in the development as epigenetic modulators. In addition, none of the currently approved peptide drugs are under investigation for their potential effects on epigenetics, hampering drug repositioning of these peptides to other indications with an epigenetic etiology.

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Section: Effects Of Epigenetics On Peptide Expressionmentioning

confidence: 99%

Peptides as epigenetic modulators: therapeutic implications

2019

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“…While several pharmacological and psychological interventions have been investigated, successful treatment to induce smoking cessation remains challenging and complex [3]. As potential therapeutic targets, several neuropeptides have been studied, e.g., proopiomelanocortin [4], brain-derived neurotrophic factor [5, 6], leptin [7], and atrial natriuretic peptide [8].…”

Section: Introductionmentioning

confidence: 99%

Methylation of the Oxytocin, Oxytocin Receptor, and Vasopressin Gene Promoters in Tobacco Use Disorder during Cessation

Proskynitopoulos,

Bleich,

Muschler

et al. 2024

Neuropsychobiology

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Introduction: Vasopressin (AVP) and oxytocin (OT) exert sex-specific effects on social pair bonding and stress reactions while also influencing craving in substance use disorders. In this regard, intranasal oxytocin (OT) and AVP antagonists present potential treatments for tobacco use disorder (TUD). Since transcription of both hormones is also regulated by gene methylation, we hypothesized sex-specific changes in methylation levels of the AVP, OT, and OT receptor (OXTR) gene during nicotine withdrawal. Methods: The study population consisted of 49 smokers (29 males, 20 females) and 51 healthy non-smokers (25 males, 26 females). Blood was drawn at day 1, day 7, and day 14 of smoking cessation. Craving was assessed with the questionnaire on smoking urges (QSU). Results: Throughout cessation, mean methylation of the OT promoter gene increased in males and decreased in females. OXTR receptor methylation decreased in females, while in males it was significantly lower at day 7. Regarding the AVP promoter, mean methylation increased in males while there were no changes in females. Using mixed linear modeling, CpG position, time point, sex, and the interaction of time point and sex as well as time point, sex, and QSU had a significant fixed effect on OT and AVP gene methylation. The interaction effect suggests that sex, time point, and QSU are interrelated, meaning that, depending on the sex, methylation could be different at different time points and vice versa. There was no significant effect of QSU on mean OXTR methylation. Discussion: We identified differences at specific CpGs between controls and smokers in OT and AVP and in overall methylation of the AVP gene. Furthermore, we found sex-specific changes in mean methylation levels of the mentioned genes throughout smoking cessation, underlining the relevance of sex in the OT and vasopressin system. This is the first study on epigenetic regulation of the OT promoter in TUD. Our results have implications for research on the utility of the AVP and OT system for treating substance craving. Future studies on both targets need to analyze their effect in the context of sex, social factors, and gene regulation.

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