Low selenium and T-2 toxin may be involved in the pathogenesis of Kashin-Beck disease by affecting AMPK/mTOR/ULK1 pathway mediated autophagy.

Autor: Deng H; Department of Occupational and Environmental Health, School of Public Health, Health Science Center, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China; Global Health Institute, Health Science Center, Xi'an Jiaotong University, Xi'an, Shaanxi 712000, China; Key Laboratory for Disease Prevention and Control and Health Promotion of Shaanxi Province, Xi'an Jiaotong University, Xi'an, Shaanxi 712000, China; Key Laboratory of Environment and Genes Related to Diseases, School of Public Health, Health Science Center, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China. Electronic address: denghuan0205@163.com., Lin X; Department of Occupational and Environmental Health, School of Public Health, Health Science Center, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China; Global Health Institute, Health Science Center, Xi'an Jiaotong University, Xi'an, Shaanxi 712000, China; Key Laboratory for Disease Prevention and Control and Health Promotion of Shaanxi Province, Xi'an Jiaotong University, Xi'an, Shaanxi 712000, China; Key Laboratory of Environment and Genes Related to Diseases, School of Public Health, Health Science Center, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China. Electronic address: linxue1997601@163.com., Xiang R; Department of Occupational and Environmental Health, School of Public Health, Health Science Center, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China; Global Health Institute, Health Science Center, Xi'an Jiaotong University, Xi'an, Shaanxi 712000, China; Key Laboratory for Disease Prevention and Control and Health Promotion of Shaanxi Province, Xi'an Jiaotong University, Xi'an, Shaanxi 712000, China; Key Laboratory of Environment and Genes Related to Diseases, School of Public Health, Health Science Center, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China. Electronic address: 17323475180@163.com., Bao M; Department of Occupational and Environmental Health, School of Public Health, Health Science Center, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China; Global Health Institute, Health Science Center, Xi'an Jiaotong University, Xi'an, Shaanxi 712000, China; Key Laboratory for Disease Prevention and Control and Health Promotion of Shaanxi Province, Xi'an Jiaotong University, Xi'an, Shaanxi 712000, China; Key Laboratory of Environment and Genes Related to Diseases, School of Public Health, Health Science Center, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China. Electronic address: 1193391597@qq.com., Qiao L; Department of Occupational and Environmental Health, School of Public Health, Health Science Center, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China; Global Health Institute, Health Science Center, Xi'an Jiaotong University, Xi'an, Shaanxi 712000, China; Key Laboratory for Disease Prevention and Control and Health Promotion of Shaanxi Province, Xi'an Jiaotong University, Xi'an, Shaanxi 712000, China; Key Laboratory of Environment and Genes Related to Diseases, School of Public Health, Health Science Center, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China. Electronic address: qlc978402409@163.com., Liu H; Department of Occupational and Environmental Health, School of Public Health, Health Science Center, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China; Global Health Institute, Health Science Center, Xi'an Jiaotong University, Xi'an, Shaanxi 712000, China; Key Laboratory for Disease Prevention and Control and Health Promotion of Shaanxi Province, Xi'an Jiaotong University, Xi'an, Shaanxi 712000, China; Key Laboratory of Environment and Genes Related to Diseases, School of Public Health, Health Science Center, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China., He H; Department of Occupational and Environmental Health, School of Public Health, Health Science Center, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China; Global Health Institute, Health Science Center, Xi'an Jiaotong University, Xi'an, Shaanxi 712000, China; Key Laboratory for Disease Prevention and Control and Health Promotion of Shaanxi Province, Xi'an Jiaotong University, Xi'an, Shaanxi 712000, China; Key Laboratory of Environment and Genes Related to Diseases, School of Public Health, Health Science Center, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China. Electronic address: hf1545767596@163.com., Wen X; Department of Occupational and Environmental Health, School of Public Health, Health Science Center, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China; Global Health Institute, Health Science Center, Xi'an Jiaotong University, Xi'an, Shaanxi 712000, China; Key Laboratory for Disease Prevention and Control and Health Promotion of Shaanxi Province, Xi'an Jiaotong University, Xi'an, Shaanxi 712000, China; Key Laboratory of Environment and Genes Related to Diseases, School of Public Health, Health Science Center, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China. Electronic address: 15736116663@163.com., Han J; Department of Occupational and Environmental Health, School of Public Health, Health Science Center, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China; Global Health Institute, Health Science Center, Xi'an Jiaotong University, Xi'an, Shaanxi 712000, China; Key Laboratory for Disease Prevention and Control and Health Promotion of Shaanxi Province, Xi'an Jiaotong University, Xi'an, Shaanxi 712000, China; Key Laboratory of Environment and Genes Related to Diseases, School of Public Health, Health Science Center, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China. Electronic address: bbbishop@126.com.
Jazyk: angličtina
Zdroj: Ecotoxicology and environmental safety [Ecotoxicol Environ Saf] 2024 Jul 01; Vol. 279, pp. 116503. Date of Electronic Publication: 2024 May 28.
DOI: 10.1016/j.ecoenv.2024.116503
Abstrakt: Kashin-Beck disease (KBD) is an endemic, environmentally associated cartilage disease. Previous studies have shown that the environmental suspected pathogenic factors of KBD, T-2 toxin and low selenium, are involved in the regulation of inflammation, oxidative stress and autophagy in some tissues and organs. In cartilage diseases, the level of cellular autophagy determines the fate of the chondrocytes. However, whether autophagy is involved in KBD cartilage lesions, and the role of low selenium and T-2 toxins in KBD cartilage injury and autophagy are still unclear. This work took the classical AMPK/mTOR/ULK1 autophagy regulatory pathway as the entry point to clarify the relationship between the environmental suspected pathogenic factors and chondrocyte autophagy. Transmission electron microscopy was used to observe the autophagy of chondrocytes in KBD patients. qRT-PCR and western blot were used to analyze the expression of AMPK/mTOR/ULK1 pathway and autophagy markers. The rat model of KBD was established by low selenium and T-2 toxin, the autophagy in rat cartilage was detected after 4- and 12-week interventions. Chondrocyte autophagy was found in KBD, and the AMPK/mTOR/ULK1 pathway was down-regulated. In the rat model, the pathway showed an up-regulated trend when low selenium and T-2 toxin, were treated for a short time or low concentration, and autophagy level increased. However, when low selenium and T-2 toxin were treated for a long time or at high concentrations, the pathway showed a down-regulated trend, and the autophagy level was reduced and even defective. In conclusion, in the process of KBD cartilage lesion, chondrocyte autophagy level may increase in the early stage, and decrease in the late stage with the progression of lesion. Low selenium and T-2 toxins may affect autophagy by AMPK/mTOR/ULK1 pathway.
Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest. All authors participated in drafting the article and critically revised important content, and endorsed the final version. Han and Deng had full access to all the data in the study and took responsibility for the integrity of the data and the accuracy of the data analysis.
(Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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