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

Yixuan Wu1,2, Qi Qu1,3,2, Zhiting Wan1,2

  • 1Department of Neurology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, China.

ACS Chemical Neuroscience
|May 19, 2023
PubMed

Insights

Fenpropathrin pesticide exposure causes Parkinson's-like symptoms by disrupting the Mdm2-p53 pathway, leading to neuroinflammation and excitotoxicity. This research clarifies the pesticide's toxic mechanism, aiding environmental protection efforts.

Area of Science:

  • Neurotoxicology
  • Environmental Health
  • Biochemistry

Background:

  • Fenpropathrin is a widely used pesticide.
  • Human exposure is linked to Parkinson's-like symptoms.
  • The specific pathogenic mechanism remains unclear.

Purpose of the Study:

  • To elucidate the pathogenic mechanism of fenpropathrin toxicity.
  • To investigate the role of the Mdm2-p53 pathway in fenpropathrin-induced neurotoxicity.

Main Methods:

  • Investigated the effects of fenpropathrin on Mdm2, p53, Nedd4L, and IL-6 expression.
  • Examined the role of Nedd4L in the ubiquitination and degradation of GLT-1.
  • Assessed glutamate accumulation and excitotoxicity.

Main Results:

  • Fenpropathrin increased murine double minute 2 (Mdm2) and decreased p53 expression.
  • Fenpropathrin stimulated neural precursor cell expressed, developmentally down-regulated 4-like (Nedd4L) and interleukin-6 (IL-6) secretion via the Mdm2-p53 pathway.
  • Nedd4L mediated glutamate transporter 1 (GLT-1) ubiquitination and degradation, causing glutamate accumulation and excitotoxicity.

Conclusions:

  • Fenpropathrin toxicity involves the Mdm2-p53 pathway, leading to Nedd4L-mediated GLT-1 degradation.
  • This mechanism contributes to neuroinflammation and excitotoxicity, explaining Parkinson's-like symptoms.
  • Findings support developing guidance for pesticide control and environmental protection.
Keywords:
GLT-1IL-6Mdm2Nedd4Lfenpropathrinp53

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