Fenpropathrin Induces GLT-1 Ubiquitination and Increases IL-6 Secretion through the Mdm2-p53 Pathway

Humanexposure to fenpropathrin, a widely used pesticide, is linkedto Parkinson's-like symptoms in the body. However, a specificpathogenic mechanism is still unclear. This study found that fenpropathrinincreased the expression of murine double minute 2 (Mdm2) and reducedthe expression of p53. Fenpropathrin stimulated the expression ofneural precursor cell expressed, developmentally down-regulated 4-like(Nedd4L) and promoted the secretion of the inflammatory cytokine interleukin-6(IL-6) through the Mdm2-p53 pathway. Nedd4L, a ubiquitin ligase, mediatedthe ubiquitination degradation of glutamate transporter 1 (GLT-1),resulting in glutamate accumulation and excitotoxicity aggravation.Our findings elucidate part of the pathogenic mechanism of fenpropathrintoxicity and provide scientific evidence to help develop guidancefor pesticide control and environmental protection.

Automated summary

The widely used pesticide fenpropathrin can increase the expression of Mdm2 and reduce the expression of p53, leading to the stimulation of Nedd4L and the secretion of IL-6 through the Mdm2-p53 pathway. Nedd4L mediates the degradation of GLT-1, resulting in glutamate accumulation and excitotoxicity aggravation. These findings provide insight into the pathogenic mechanism of fenpropathrin toxicity and contribute to the development of guidance for pesticide control and environmental protection.