Mechanism of miR-143 regulating ERK5 signaling pathway-mediated manganese-induced striatal neuronal apoptosis

Huan Mao1, Yidan Wei2, Cheng Liu2

  • 1Zunyi Medical University School of Public Health, Zunyi, Guizhou 563000, China; Chongqing Yuzhong District Center for Disease Control and Prevention, Chongqing 400010, China.

Insights

High manganese exposure increases miR-143, a microRNA that promotes neuronal apoptosis by inhibiting the ERK5 pathway. This finding reveals a key mechanism in manganese neurotoxicity.

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Toxicology

Background:

  • Manganese overexposure can cause neurotoxicity and neuronal apoptosis.
  • MicroRNAs (miRNAs) play a significant role in the apoptotic processes of neurons.

Purpose of the Study:

  • To investigate the role of miRNAs in manganese-induced neuronal apoptosis.
  • To identify potential miRNA targets involved in this process.

Main Methods:

  • Assessed miR-143 expression in the striatum following high-dose manganese exposure.
  • Upregulated miR-143 expression stereotaxically in striatal neurons.
  • Investigated the regulatory relationship between miR-143 and the ERK5 signaling pathway.
  • Measured mRNA levels of ERK5, Bax, and Caspase-3.

Main Results:

  • miR-143 expression was elevated in the striatum after manganese exposure.
  • Overexpression of miR-143 promoted apoptosis in striatal neurons.
  • miR-143 negatively regulated ERK5, decreasing its mRNA levels and inhibiting the ERK5 signaling pathway.
  • Inhibition of ERK5 increased Bax and Caspase-3 expression, exacerbating neuronal apoptosis.

Conclusions:

  • Overexpression of miR-143 inhibits the ERK5 signaling pathway.
  • miR-143 promotes manganese-induced apoptosis in striatal neurons.
  • This study elucidates a molecular mechanism underlying manganese neurotoxicity.