Soot nanoparticles promote ferroptosis in dopaminergic neurons via alteration of m6A RNA methylation in Parkinson’s disease

帕金森病 多巴胺能 甲基化 RNA甲基化 化学 核糖核酸 疾病 环境化学 生物 基因 多巴胺 生物化学 神经科学 医学 内科学 甲基转移酶
作者
Jiezhu Feng,Piao Zhang,Kunlin Chen,Peiting Huang,Xiaomei Liang,Jiawei Dong,Baoyu Zhu,Zhongling Fu,Tongtong Deng,Linyan Zhu,Chengyu Chen,Yuhu Zhang
出处
期刊:Journal of Hazardous Materials [Elsevier]
卷期号:473: 134691-134691 被引量:5
标识
DOI:10.1016/j.jhazmat.2024.134691
摘要

Soot nanoparticles (SNPs) are black carbon prevalent in atmospheric environment with significant impacts on public health, leading to neurodegenerative diseases including development of Parkinson's disease (PD). This study investigated the effects of SNPs exposure on PD symptoms, employing both in vivo and in vitro PD models. In the in vivo experiments, animal behavior assessments showed that SNPs exposure exacerbated motor and cognitive impairments in PD mice. Molecular biology techniques further unveiled that SNPs aggravated degeneration of dopaminergic neurons. In vitro experiments revealed that SNPs exposure intensified ferroptosis of PD cells by increasing reactive oxygen species and iron ion levels, while reducing glutathione levels and mitochondrial membrane potential. Sequencing tests indicated elevated N6-methyladenosine (m6A) alteration of the ferroptosis-related protein, acyl-CoA synthetase long chain family member 4 (ACSL4). This study demonstrates that SNPs may exacerbate the onset and progression of PD by recruiting YTH domain-containing family protein 1 (YTHDF1) protein, enhancing m6A methylation in the ACSL4 5'UTR, amplifying ACSL4 protein expression, and accelerating the ferroptosis process in dopaminergic neurons. These molecular mechanisms underlying SNPs exacerbation of PD development may provide crucial insights for formulating environmental safety regulations and potential therapeutic strategies addressing PD in populations residing in regions with varied air quality. Soot nanoparticles (SNPs) are black carbon prevalent in atmospheric environment with significant impacts on human health. Exposure to SNPs is associated with heightened risks of neurodegenerative diseases including Parkinson's disease (PD). Understanding the impact of SNPs on PD development and associated molecular mechanisms is crucial for assessing these health risks. This study demonstrates that SNPs exposure may exacerbate PD by recruiting YTHDF1 protein, enhancing m6A methylation in ACSL4 5'UTR, amplifying ACSL4 protein expression, and accelerating ferroptosis process in dopaminergic neurons. Insights into the molecular mechanisms underlying SNPs exacerbation of PD development could offer critical guidance for establishing environmental safety regulations.
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