1. Academic Validation
  2. 1,2-Dichloroethane induces apoptosis in the cerebral cortexes of NIH Swiss mice through microRNA-182-5p targeting phospholipase D1 via a mitochondria-dependent pathway

1,2-Dichloroethane induces apoptosis in the cerebral cortexes of NIH Swiss mice through microRNA-182-5p targeting phospholipase D1 via a mitochondria-dependent pathway

  • Toxicol Appl Pharmacol. 2021 Nov 1;430:115728. doi: 10.1016/j.taap.2021.115728.
Boxuan Liang 1 Yizhou Zhong 1 Bo Wang 1 Li Lin 1 Jun Liu 1 Xi Lin 1 Yuji Huang 1 Manjiang Hu 1 Bingli Zhang 1 Hao Meng 1 Liang Jiang 2 Junying Jiang 3 Jiejiao Wu 4 Yating Zhang 3 Weifeng Rong 4 Xingfen Yang 5 Zhenlie Huang 6
Affiliations

Affiliations

  • 1 NMPA Key Laboratory for Safety Evaluation of Cosmetics, Guangdong Provincial Key Laboratory of Tropical Disease Research, Department of Toxicology, School of Public Health, Southern Medical University, Guangzhou 510515, China.
  • 2 Department of Toxicology, Guangdong Provincial Hospital for Occupational Disease Prevention and Treatment, Guangzhou 510300, China; Department of Toxicology, Faculty of Preventive Medicine, School of Public Health, Sun Yat-sen University, Guangzhou 510080, China.
  • 3 Faculty of Preventive Medicine, School of Public Health, Guangdong Pharmaceutical University, Guangzhou 510006, China.
  • 4 Department of Toxicology, Guangdong Provincial Hospital for Occupational Disease Prevention and Treatment, Guangzhou 510300, China.
  • 5 Food Safety and Health Research Center, School of Public Health, Southern Medical University, Guangzhou 510515, China.
  • 6 NMPA Key Laboratory for Safety Evaluation of Cosmetics, Guangdong Provincial Key Laboratory of Tropical Disease Research, Department of Toxicology, School of Public Health, Southern Medical University, Guangzhou 510515, China. Electronic address: [email protected].
Abstract

1,2-Dichloroethane (1,2-DCE) is a pervasive environmental pollutant found in ambient and residential air, as well as ground and drinking water. Overexposure to it results in cortex edema, in both Animals and humans. 1,2-DCE induces Apoptosis in the cerebellum, liver and testes. This promotes the hypothesis that 1,2-DCE may induce Apoptosis in the cortex as brain edema progresses. To validate our hypothesis, 40 NIH male mice were exposed to 0, 100, 350, 700 mg/m3 1,2-DCE by whole-body dynamic inhalation for 28 consecutive days. MicroRNA (miRNA) and mRNA microarray combined with TdT-mediated dUTP nick-end labeling, flow cytometry, and mitochondrial membrane potential (mtΔΨ) measurement were applied to identify the cortex Apoptosis pathways' specific responses to 1,2-DCE, in vitro and in vivo. The results showed that 1,2-DCE caused brain edema and increased Apoptosis in the mouse cortexes. We confirmed that 1,2-DCE induced increased Apoptosis via mitochondrial pathway, both in vitro and in vivo, as evidenced by increased Caspase-3, cleaved Caspase-3, Cytochrome c and Bax expression, and decreased Bcl-2 expression. Additionally, mtΔΨ decreased after 1,2-DCE treatment in vitro. 1,2-DCE exposure increased miR-182-5p and decreased Phospholipase D1 (PLD1) in the cerebral cortex of mice. MiR-182-5p overexpression and PLD1 inhibition reduced mtΔΨ and increased astrocyte Apoptosis, yet miR-182-5p inhibition alleviated the 1,2-DCE-induced PLD1 down-regulation and the increased Apoptosis. Finally, PLD1 was confirmed to be a target of miR-182-5p by luciferase assay. Taken together, our findings indicate that 1,2-DCE exposure induces Apoptosis in the cortex via a mitochondria-dependent pathway. This pathway is regulated by a miR-182-5p⊣PLD1 axie.

Keywords

1,2-Dichloroethane; MiR-182-5p; Mitochondrial apoptosis; Neurotoxicity; Phospholipase D1.

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  • HY-P0081
    98.28%, Bcl-2 Family Inhibitor