3-Monochloropropane-1,2-diol esters induce HepG2 cells necroptosis via CTSB/TFAM/ROS pathway

Shuang Guan; Xiao Qu; Jianfeng Wang; Duoduo Zhang; Jing Lu

doi:10.1016/j.fct.2024.114525

3-Monochloropropane-1,2-diol esters induce HepG2 cells necroptosis via CTSB/TFAM/ROS pathway

Food Chem Toxicol. 2024 Apr:186:114525. doi: 10.1016/j.fct.2024.114525. Epub 2024 Feb 24.

Authors

Shuang Guan¹, Xiao Qu², Jianfeng Wang³, Duoduo Zhang⁴, Jing Lu⁵

Affiliations

¹ College of Food Science and Engineering, Jilin University, Changchun, Jilin, 130062, People's Republic of China; Key Laboratory of Zoonosis, Ministry of Education College of Veterinary Medicine, Jilin University, Changchun, Jilin, 130062, People's Republic of China.
² College of Food Science and Engineering, Jilin University, Changchun, Jilin, 130062, People's Republic of China.
³ Key Laboratory of Zoonosis, Ministry of Education College of Veterinary Medicine, Jilin University, Changchun, Jilin, 130062, People's Republic of China.
⁴ Department of Thoracic Surgery, The First Hospital of Jilin University, Changchun, Jilin, 130021, People's Republic of China. Electronic address: ddzhang@jlu.edu.cn.
⁵ College of Food Science and Engineering, Jilin University, Changchun, Jilin, 130062, People's Republic of China; Key Laboratory of Zoonosis, Ministry of Education College of Veterinary Medicine, Jilin University, Changchun, Jilin, 130062, People's Republic of China. Electronic address: Lu_jing@jlu.edu.cn.

PMID: 38408632
DOI: 10.1016/j.fct.2024.114525

Abstract

3-monochloropropane-1,2-diol esters (3-MCPDE) are toxic substances that form in food thermal processing and have a diverse range of toxicities. In this study, we found that 3-MCPDE triggered necroptosis by RIPK1/RIPK3/MLKL pathway in HepG2 cells. Previous studies have shown that ROS is an important activator of RIPK1 and RIPK3. The data showed that 3-MCPDE induced excessive ROS production through mitochondrial damage. After treatment with ROS inhibitor N-acetylcysteine (NAC), 3-MCPDE-induced necroptosis was relieved. Further, we explored how 3-MCPDE destroys mitochondria. The data suggested that 3-MCPDE induced mitochondrial dysfunction through the CTSB/TFAM pathway. Overall, the results indicated that 3-MCPDE induced necroptosis through CTSB/TFAM/ROS pathway in HepG2 cells. Our study provided a new mechanism for 3-MCPDE hepatotoxicity.

Keywords: 3-MCPDE; CTSB; HepG2 cells; Necroptosis; ROS.

MeSH terms

Esters / toxicity
Hep G2 Cells
Humans
Necroptosis
Reactive Oxygen Species / metabolism
Receptor-Interacting Protein Serine-Threonine Kinases / metabolism
alpha-Chlorohydrin* / analogs & derivatives*
alpha-Chlorohydrin* / toxicity

Substances

3-monochloropropane-1, 2 diol ester
alpha-Chlorohydrin
Reactive Oxygen Species
Esters
Receptor-Interacting Protein Serine-Threonine Kinases