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
  • 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: [email protected].
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.
Products