UBE2L3 promotes benzene-induced hematotoxicity via autophagy-dependent ferroptosis.

Autor: Wang B; Jiangsu Provincial Center for Disease Prevention and Control, Nanjing, Jiangsu 210000, China; Key Laboratory of Environmental Medicine Engineering of Ministry of Education, School of Public Health, Southeast University, Nanjing, Jiangsu 210009, China., Li F; Jiangsu Provincial Center for Disease Prevention and Control, Nanjing, Jiangsu 210000, China., Hu J; Jiangsu Provincial Center for Disease Prevention and Control, Nanjing, Jiangsu 210000, China; Key Laboratory of Environmental Medicine Engineering of Ministry of Education, School of Public Health, Southeast University, Nanjing, Jiangsu 210009, China., Sun F; Jiangsu Provincial Center for Disease Prevention and Control, Nanjing, Jiangsu 210000, China; Key Laboratory of Environmental Medicine Engineering of Ministry of Education, School of Public Health, Southeast University, Nanjing, Jiangsu 210009, China., Han L; Jiangsu Provincial Center for Disease Prevention and Control, Nanjing, Jiangsu 210000, China; Key Laboratory of Environmental Medicine Engineering of Ministry of Education, School of Public Health, Southeast University, Nanjing, Jiangsu 210009, China., Zhang J; Jiangsu Provincial Center for Disease Prevention and Control, Nanjing, Jiangsu 210000, China; Key Laboratory of Environmental Medicine Engineering of Ministry of Education, School of Public Health, Southeast University, Nanjing, Jiangsu 210009, China. Electronic address: 101011288@seu.edu.cn., Zhu B; Jiangsu Provincial Center for Disease Prevention and Control, Nanjing, Jiangsu 210000, China; Key Laboratory of Environmental Medicine Engineering of Ministry of Education, School of Public Health, Southeast University, Nanjing, Jiangsu 210009, China. Electronic address: zhubl@jscdc.cn.
Jazyk: angličtina
Zdroj: Ecotoxicology and environmental safety [Ecotoxicol Environ Saf] 2024 Sep 15; Vol. 283, pp. 116773. Date of Electronic Publication: 2024 Jul 26.
DOI: 10.1016/j.ecoenv.2024.116773
Abstrakt: Benzene is a common environmental pollutant and significant health hazard. Low-dose benzene exposure is common in most industrial settings, and some workers exhibit hematotoxicity characterized by impaired hematopoietic function. Consequently, understanding the early hematopoietic damage and biomarkers associated with low-dose benzene exposure is of critical importance for health risk assessment. Using data from a 5-year prospective cohort study on benzene exposure and the National Center for Biotechnology Information's Gene Expression Omnibus database, we detected significant downregulation of the ubiquitin-conjugating enzyme UBE2L3 (E2) in benzene-exposed subjects compared to control subjects. Liquid chromatography tandem mass spectrometry and co-immunoprecipitation experiments illustrated the binding interaction between UBE2L3 and the ubiquitin-protein ligase ZNF598 (E3). We applied deep learning algorithms to predict candidate interacting proteins and then conducted validation via co-immunoprecipitation experiments, which showed that ZNF598 engages in binding with the autophagy protein LAMP-2. Subsequent overexpression and knockdown of UBE2L3 coupled with immunofluorescence experiments and transmission electron microscopy revealed that UBE2L3 disrupts the ubiquitination-degradation of LAMP-2 by ZNF598, reduces GPX4 expression levels, and activates an autophagy-dependent ferroptosis pathway. It also leads to increased lipid peroxidation, thereby promoting ferroptosis and contributing to the hematotoxicity induced by benzene. In summary, our results suggest that UBE2L3 may be involved in early hematopoietic damage by modulating the autophagy-dependent ferroptosis signaling pathway in benzene-induced hematotoxicity.
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 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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