Role of oxidative stress and DNA hydroxymethylation in the neurotoxicity of fine particulate matter.

Abstract

Epidemiological studies have implicated fine particulate matter (PM2.5) as a risk factor for neurodegenerative diseases and neurodevelopmental disorders. However, the underlying molecular mechanisms and the influences of different components remain largely elusive. Here, we extended our previous work to investigate the role of oxidative stress and DNA hydroxymethylation in neuronal pathology of PM2.5. We found PM2.5 and its extracts (water-soluble extracts, organic extracts and carbon core component) differentially caused cell cycle arrest, cell apoptosis and the cell proliferation inhibition in neuronal cells. These effects were mechanistically related to each other and oxidative stress, suggesting PM2.5 and toxic compounds adsorbed on the particles may cause different types of brain damages. In addition, PM2.5 and its organic extracts increased global DNA hydroxymethylation and gene-specific DNA hydroxymethylation of neuronal genes, and subsequently interfered with their mRNA expression. The impairments in neuronal progression characterized with decreased length of neurite and reduced mRNA expression of neuronal markers and synaptic markers. The blocking effects of antioxidants demonstrated the involvement of oxidative stress-mediated hydroxymethylation abnormalities in PM2.5-induced defects in neurite outgrowth and synapse formation. Our results first revealed the role of oxidative stress-mediated abnormal DNA hydroxymethylation in neuronal impairments of PM2.5, and thoroughly evaluated the neurocytotoxicity of different components.

• Authors: Hongying Wei, Yan Feng, Fan Liang, Wei Cheng, Xiaomeng Wu, Ren Zhou, Yan Wang
• Journal: Toxicology (Toxicology) Vol. 380 Pg. 94-103 (04 01 2017) ISSN: 1879-3185 [Electronic] Ireland
• PMID: 28153600 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2017 Elsevier B.V. All rights reserved.

Chemical References

• Neurotoxins
• Particulate Matter
• RNA, Messenger
• Reactive Oxygen Species

Topics

• Apoptosis (drug effects)
• Cell Cycle Checkpoints (drug effects)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• DNA Methylation (drug effects)
• Humans
• Neurons (cytology, drug effects)
• Neurotoxins (toxicity)
• Oxidative Stress (drug effects)
• Particulate Matter (toxicity)
• RNA, Messenger (genetics, metabolism)
• Reactive Oxygen Species (metabolism)