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  3. MEK1 inhibition ameliorates mitochondrial-dependent apoptosis induced by deltamethrin in mouse hippocampal neuron HT22 cells

MEK1 inhibition ameliorates mitochondrial-dependent apoptosis induced by deltamethrin in mouse hippocampal neuron HT22 cells

  • Toxicol In Vitro. 2025 Mar 7:106:106047. doi: 10.1016/j.tiv.2025.106047.
Lexing Wei 1,  Yang Chen 1,  Minjia Wu 1,  Peixuan Ma 1,  Huan Wang 2,  Yueming Jiang 1,  Michael Aschner 3,  Jing Zhou 4,  Guodong Lu 5,  Lina Zhao 6,  Xiaowei Huang 7
Affiliations

Affiliations

  • 1 Department of Toxicology, School of Public Health, Guangxi Key Laboratory of Environment and Health Research, Guangxi Medical University, Nanning 530021, China; Guangxi Colleges and Universities Key Laboratory of Prevention and Control of Highly Prevalent Diseases, Guangxi Medical University, Nanning 530021, China.
  • 2 Department of Toxicology, School of Public Health, Guangxi Key Laboratory of Environment and Health Research, Guangxi Medical University, Nanning 530021, China.
  • 3 Department of Molecular Pharmacology at Albert Einstein College of Medicine, Bronx, NY 10461, USA.
  • 4 School of Preclinical Medicine, Guangxi Medical University, Nanning 530021, China.
  • 5 Department of Toxicology, School of Public Health, Guangxi Key Laboratory of Environment and Health Research, Guangxi Medical University, Nanning 530021, China; School of Public Health, Fudan University, Shanghai 200032, China.
  • 6 School of Public Health, Wuhan University, Wuhan 430071, China.
  • 7 Department of Toxicology, School of Public Health, Guangxi Key Laboratory of Environment and Health Research, Guangxi Medical University, Nanning 530021, China; Guangxi Colleges and Universities Key Laboratory of Prevention and Control of Highly Prevalent Diseases, Guangxi Medical University, Nanning 530021, China. Electronic address: huangxiaowei@sr.gxme.edu.cn.
PMID: 40058615 DOI: 10.1016/j.tiv.2025.106047
Abstract

Deltamethrin (DM), a widely used pyrethroid insecticide, has been increasingly recognized as a risk factor for neurodegeneration. However, the underlying mechanism is still far from clear. In this study, we investigated whether MEK1 is involved in DM-induced neurotoxicity and mediated mitochondrial-dependent Apoptosis. In mouse hippocampal neuron HT22 cells model, DM (2,10,50 μM) dose-dependently increased apoptotic cells rate and impaired mitochondrial membrane potential (MMP), as well as significantly upregulated of apoptotic related proteins Bax, cytochrome c (Cyt-c) and Caspase-3 were observed. RNA-sequencing analysis further revealed that the MEK/ERK signal pathway was remarkably enriched and activated after DM exposure. In particularly, upregulation of MEK1, Other than ERK1/2, was detected at both transcriptional and translational levels. Inhibition of MEK1 can effectively result in the recovery of mitochondrial morphology and MMP in DM-treated HT22 cells. And that further alleviated Apoptosis by reversing the overexpression of Bax, Cyt-c and Caspase-3. Collectively, these findings demonstrate the critical role of MEK1 in regulating mitochondrial-dependent Apoptosis induced by DM, providing a novel understanding of the neurotoxicity of DM.

Keywords

Deltamethrin; MAPK signal pathway; MEK1; Mitochondrial-dependent apoptosis; Neurotoxicity.

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