Paraquat-induced oxidative stress regulates N6-methyladenosine (m6A) modification of long noncoding RNAs in Neuro-2a cells

Qianqian Su; Nengzhou Chen; Jianping Tang; Junxiang Wang; Wei-Chun Chou; Fuli Zheng; Wenya Shao; Guangxia Yu; Ping Cai; Zhenkun Guo; Minghua He; Huangyuan Li; Siying Wu

doi:10.1016/j.ecoenv.2022.113503

Paraquat-induced oxidative stress regulates N6-methyladenosine (m⁶A) modification of long noncoding RNAs in Neuro-2a cells

Ecotoxicol Environ Saf. 2022 Jun 1:237:113503. doi: 10.1016/j.ecoenv.2022.113503. Epub 2022 Apr 19.

Authors

Qianqian Su¹, Nengzhou Chen¹, Jianping Tang¹, Junxiang Wang¹, Wei-Chun Chou², Fuli Zheng³, Wenya Shao³, Guangxia Yu³, Ping Cai⁴, Zhenkun Guo⁵, Minghua He⁶, Huangyuan Li⁷, Siying Wu⁸

Affiliations

¹ Department of Preventive Medicine, School of Public Health, Fujian Medical University, Fuzhou 350122, China.
² Department of Environmental and Global Health and Center for Environmental and Human Toxicology, College of Public Health and Health Professions, University of Florida, Gainesville, FL, USA.
³ Department of Preventive Medicine, School of Public Health, Fujian Medical University, Fuzhou 350122, China; The Key Laboratory of Environment and Health, School of Public Health, Fujian Medical University, Fuzhou 350122, China; Fujian Provincial Key Laboratory of Environment Factors and Cancer, School of Public Health, Fujian Medical University, Fuzhou 350122, China.
⁴ Department of Environmental and Global Health and Center for Environmental and Human Toxicology, College of Public Health and Health Professions, University of Florida, Gainesville, FL, USA; The Key Laboratory of Environment and Health, School of Public Health, Fujian Medical University, Fuzhou 350122, China; Department of Health Inspection and Quarantine, School of Public Health, Fujian Medical University, Fuzhou 350122, China.
⁵ The Key Laboratory of Environment and Health, School of Public Health, Fujian Medical University, Fuzhou 350122, China; Fujian Provincial Key Laboratory of Environment Factors and Cancer, School of Public Health, Fujian Medical University, Fuzhou 350122, China.
⁶ The Key Laboratory of Environment and Health, School of Public Health, Fujian Medical University, Fuzhou 350122, China; Fujian Provincial Key Laboratory of Environment Factors and Cancer, School of Public Health, Fujian Medical University, Fuzhou 350122, China. Electronic address: mhhe@fjmu.edu.cn.
⁷ Department of Preventive Medicine, School of Public Health, Fujian Medical University, Fuzhou 350122, China; The Key Laboratory of Environment and Health, School of Public Health, Fujian Medical University, Fuzhou 350122, China; Fujian Provincial Key Laboratory of Environment Factors and Cancer, School of Public Health, Fujian Medical University, Fuzhou 350122, China. Electronic address: lhy@fjmu.edu.cn.
⁸ Department of Epidemiology and Health Statistics, School of Public Health, Fujian Medical University, Fuzhou 350122, China; Fujian Provincial Key Laboratory of Environment Factors and Cancer, School of Public Health, Fujian Medical University, Fuzhou 350122, China. Electronic address: sywu@fjmu.edu.cn.

PMID: 35453019
DOI: 10.1016/j.ecoenv.2022.113503

Abstract

Paraquat (PQ) is a ubiquitously applied herbicide. Long-term PQ exposure with low dose has been reported to induce abnormal expression of long non-coding RNAs (lncRNAs) in brain nerve cells, which could further lead to Parkinson's disease (PD). N6-methyladenosine (m⁶A) modification has recently been identified as having an important role in regulating the function of lncRNAs. However, how m⁶A modification regulates lncRNAs following PQ exposure remains largely unknown. Herein, this study reported m⁶A modification of lncRNAs in mouse neuroblastoma cells (Neuro-2a) following PQ induced reactive oxide species (ROS). M⁶A sequencing was performed to explore the m⁶A modificated pattern of lncRNAs in Neuro-2a cells which were treated with 200 μM PQ for 3 h. It was found that PQ hypermethylated total RNA and changed the expression of m⁶A methyltransferase and demethylase proteins, which leading to the alteration of m⁶A modification of lncRNAs. Furthermore, the functional analysis further revealed that N-acetyl-L-cysteine (NAC)，a ROS scavengers, partly reversed PQ-induced distinct m⁶A modificated pattern of lncRNAs. In addition, tow specific m⁶A modified lncRNAs were identified: cell division cycle 5-like (lncRNA CDC5L) and signal transducer and activator of transcription 3 (lncRNA STAT3), which could influence downstream autophagy related biological function. In summary, this work could potentially contribute to the new insight of lncRNAs m⁶A modification mechanism in the field of environmental toxicology.

Keywords: LncRNAs; M(6)A methylation; Paraquat; Parkinson’s disease; ROS.

MeSH terms

Adenosine / analogs & derivatives
Adenosine / metabolism
Animals
Mice
Oxidative Stress / genetics
Paraquat* / toxicity
RNA, Long Noncoding* / genetics
RNA, Long Noncoding* / metabolism
Reactive Oxygen Species / metabolism

Substances

RNA, Long Noncoding
Reactive Oxygen Species
N-methyladenosine
Adenosine
Paraquat