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

摘要

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.

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