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

Authors：Wu, Yixuan; Qu, Qi; Wan, Zhiting; Qu, Shaogang^*

Source：ACS Chemical Neuroscience, 2023, 14(11): 2112-2122.

DOI：10.1021/acschemneuro.3c00112

• GLT-1
• Nedd4L
• Mdm2
• p53
• IL-6
• fenpropathrin

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.

• Institution
  Southern Medical University