The regulatory role of miR-21 in ferroptosis by targeting FTH1 and the contribution of microglia-derived miR-21 in exosomes to arsenic-induced neuronal ferroptosis.

Autor: Wang H; Key Laboratory of Environmental Stress and Chronic Disease Control and Prevention, Ministry of Education, China Medical University, Shenyang, Liaoning, China, 110122; The Key Laboratory of Liaoning Province on Toxic and Biological Effects of Arsenic, China Medical University, Shenyang, Liaoning, China, 110122; Department of Occupational Health, School of Public Health, China Medical University, Shenyang, Liaoning, China, 110122., Liu X; Key Laboratory of Environmental Stress and Chronic Disease Control and Prevention, Ministry of Education, China Medical University, Shenyang, Liaoning, China, 110122; The Key Laboratory of Liaoning Province on Toxic and Biological Effects of Arsenic, China Medical University, Shenyang, Liaoning, China, 110122; Department of Occupational Health, School of Public Health, China Medical University, Shenyang, Liaoning, China, 110122., Chen Y; Key Laboratory of Environmental Stress and Chronic Disease Control and Prevention, Ministry of Education, China Medical University, Shenyang, Liaoning, China, 110122; The Key Laboratory of Liaoning Province on Toxic and Biological Effects of Arsenic, China Medical University, Shenyang, Liaoning, China, 110122; Department of Occupational Health, School of Public Health, China Medical University, Shenyang, Liaoning, China, 110122., Li W; Key Laboratory of Environmental Stress and Chronic Disease Control and Prevention, Ministry of Education, China Medical University, Shenyang, Liaoning, China, 110122; The Key Laboratory of Liaoning Province on Toxic and Biological Effects of Arsenic, China Medical University, Shenyang, Liaoning, China, 110122; Department of Occupational Health, School of Public Health, China Medical University, Shenyang, Liaoning, China, 110122., Ge Y; Key Laboratory of Environmental Stress and Chronic Disease Control and Prevention, Ministry of Education, China Medical University, Shenyang, Liaoning, China, 110122; The Key Laboratory of Liaoning Province on Toxic and Biological Effects of Arsenic, China Medical University, Shenyang, Liaoning, China, 110122; Department of Occupational Health, School of Public Health, China Medical University, Shenyang, Liaoning, China, 110122., Liang H; Key Laboratory of Environmental Stress and Chronic Disease Control and Prevention, Ministry of Education, China Medical University, Shenyang, Liaoning, China, 110122; The Key Laboratory of Liaoning Province on Toxic and Biological Effects of Arsenic, China Medical University, Shenyang, Liaoning, China, 110122; Department of Occupational Health, School of Public Health, China Medical University, Shenyang, Liaoning, China, 110122., Xu B; Key Laboratory of Environmental Stress and Chronic Disease Control and Prevention, Ministry of Education, China Medical University, Shenyang, Liaoning, China, 110122; Department of Environmental Health, School of Public Health, China Medical University, Shenyang, Liaoning, China, 110122. Electronic address: bxu10@cmu.edu.cn., Li X; Key Laboratory of Environmental Stress and Chronic Disease Control and Prevention, Ministry of Education, China Medical University, Shenyang, Liaoning, China, 110122; The Key Laboratory of Liaoning Province on Toxic and Biological Effects of Arsenic, China Medical University, Shenyang, Liaoning, China, 110122; Department of Occupational Health, School of Public Health, China Medical University, Shenyang, Liaoning, China, 110122. Electronic address: xli75@cmu.edu.cn.
Jazyk: angličtina
Zdroj: Journal of hazardous materials [J Hazard Mater] 2024 Oct 05; Vol. 478, pp. 135580. Date of Electronic Publication: 2024 Aug 22.
DOI: 10.1016/j.jhazmat.2024.135580
Abstrakt: Arsenic is recognized as a hazardous environmental toxicant strongly associated with neurological damage, but the mechanism is ambiguous. Neuronal cell death is one of the mechanisms of arsenic-induced neurological injury. Ferroptosis is involved in the pathophysiological process of many neurological diseases, however, the role and regulatory mechanism of ferroptosis in nerve injury under arsenic exposure remains uncovered. Our findings confirmed the role of ferroptosis in arsenic-induced learning and memory disorder and revealed miR-21 played a regulatory role in neuronal ferroptosis. Further study discovered that miR-21 regulated neuronal ferroptosis by targeting at FTH1, a finding which has not been documented before. We also found an extra increase of ferroptosis in neuronal cells conditionally cultured by medium collected from arsenic-exposed microglial cells when compared with neuronal cells directly exposed to the same dose of arsenic. Moreover, microglia-derived exosomes removal or miR-21 knockdown in microglia inhibited neuronal ferroptosis, suggesting the role of intercellular communication in the promotion of neuronal ferroptosis. In summary, our findings highlighted the regulatory role of miR-21 in ferroptosis and the contribution of microglia-derived miR-21 in exosomes to arsenic-induced neuronal ferroptosis.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
Externí odkaz: