Academic Journal

DNA Hypomethylation Is Associated with Increased Inflammation in Peripheral Blood Neutrophils of Children with Autism Spectrum Disorder: Understanding the Role of Ubiquitous Pollutant Di(2-ethylhexyl) Phthalate

التفاصيل البيبلوغرافية
العنوان: DNA Hypomethylation Is Associated with Increased Inflammation in Peripheral Blood Neutrophils of Children with Autism Spectrum Disorder: Understanding the Role of Ubiquitous Pollutant Di(2-ethylhexyl) Phthalate
المؤلفون: Ali A. Alshamrani, Samiyah Alshehri, Sana S. Alqarni, Sheikh F. Ahmad, Hanan Alghibiwi, Naif O. Al-Harbi, Saleh A. Alqarni, Laila Y. Al-Ayadhi, Sabry M. Attia, Ali S. Alfardan, Saleh A. Bakheet, Ahmed Nadeem
المصدر: Metabolites, Vol 13, Iss 3, p 458 (2023)
بيانات النشر: MDPI AG, 2023.
سنة النشر: 2023
المجموعة: LCC:Microbiology
مصطلحات موضوعية: ASD, environmental pollutant, neutrophils, DNMT1, DNA methylation, Microbiology, QR1-502
الوصف: Autism spectrum disorder (ASD) is a multidimensional disorder in which environmental, immune, and genetic factors act in concert to play a crucial role. ASD is characterized by social interaction/communication impairments and stereotypical behavioral patterns. Epigenetic modifications are known to regulate genetic expression through various mechanisms. One such mechanism is DNA methylation, which is regulated by DNA methyltransferases (DNMTs). DNMT transfers methyl groups onto the fifth carbon atom of the cytosine nucleotide, thus converting it into 5-methylcytosine (5mC) in the promoter region of the DNA. Disruptions in methylation patterns of DNA are usually associated with modulation of genetic expression. Environmental pollutants such as the plasticizer Di(2-ethylhexyl) phthalate (DEHP) have been reported to affect epigenetic mechanisms; however, whether DEHP modulates DNMT1 expression, DNA methylation, and inflammatory mediators in the neutrophils of ASD subjects has not previously been investigated. Hence, this investigation focused on the role of DNMT1 and overall DNA methylation in relation to inflammatory mediators (CCR2, MCP-1) in the neutrophils of children with ASD and typically developing healthy children (TDC). Further, the effect of DEHP on overall DNA methylation, DNMT1, CCR2, and MCP-1 in the neutrophils was explored. Our results show that the neutrophils of ASD subjects have diminished DNMT1 expression, which is associated with hypomethylation of DNA and increased inflammatory mediators such as CCR2 and MCP-1. DEHP further causes downregulation of DNMT1 expression in the neutrophils of ASD subjects, probably through oxidative inflammation, as antioxidant treatment led to reversal of a DEHP-induced reduction in DNMT1. These data highlight the importance of the environmental pollutant DEHP in the modification of epigenetic machinery such as DNA methylation in the neutrophils of ASD subjects.
نوع الوثيقة: article
وصف الملف: electronic resource
اللغة: English
تدمد: 2218-1989
Relation: https://www.mdpi.com/2218-1989/13/3/458; https://doaj.org/toc/2218-1989
DOI: 10.3390/metabo13030458
URL الوصول: https://doaj.org/article/fbb35eb03af245fb9cd5eaac1f1f52d3
رقم الانضمام: edsdoj.fbb35eb03af245fb9cd5eaac1f1f52d3
قاعدة البيانات: Directory of Open Access Journals
الوصف
تدمد:22181989
DOI:10.3390/metabo13030458