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Role of p53 methylation in manganese-induced cyclooxygenase-2 expression in BV2 microglial cells

Xiaoling Liu1, Chunyan Yao1, Yan Tang2

  • 1Department of Epidemiology, College of Preventive Medicine, Army Medical University (Third Military Medical University), Chongqing, China.

Ecotoxicology and Environmental Safety
|September 7, 2022
PubMed

Insights

Excess manganese exposure triggers neuroinflammation by inhibiting p53, leading to increased microglial cyclooxygenase-2 (COX-2) expression. This study reveals manganese-induced DNA methylation as a key mechanism driving neurodegeneration.

Area of Science:

  • Neuroscience
  • Environmental Health
  • Molecular Biology

Background:

  • Manganese (Mn) is essential but toxic in excess, linked to neurodegeneration.
  • Microglial cyclooxygenase-2 (COX-2) overexpression drives neuroinflammation in disease.
  • Mn exposure is suspected to induce neuroinflammation via COX-2, but mechanisms are unclear.

Purpose of the Study:

  • To investigate the role of p53 in manganese-induced COX-2 expression in microglial cells.
  • To elucidate the molecular mechanisms underlying Mn-induced neuroinflammation.

Main Methods:

  • Exposure of BV2 microglial cells to manganese (Mn).
  • Analysis of COX-2 and p53 expression levels.
  • Manipulation of p53 activity using activators and overexpression.
  • Assessment of DNA methylation patterns of p53 using a demethylation reagent (5-Aza-dC).

Main Results:

  • Mn exposure upregulated COX-2 and downregulated p53 in microglial cells.
  • p53 activation or overexpression inhibited Mn-induced COX-2 and prostaglandin E2 (PGE2) production.
  • Mn exposure increased p53 DNA methylation.
  • Demethylation treatment restored p53 expression and reduced COX-2 levels.

Conclusions:

  • Mn inhibits p53 expression in microglia, potentially through DNA methylation.
  • This p53 inhibition leads to increased COX-2 expression and neuroinflammation.
  • Targeting p53 or DNA methylation may offer therapeutic strategies for Mn-induced neurotoxicity.
Keywords:
Cyclooxygenase-2InflammationManganeseMethylationMicrogliaP53

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