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

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.