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RTP801 regulates maneb- and mancozeb-induced cytotoxicity via NF-κB

Shu-Yuan Cheng1, Seon Oh, Marcela Velasco

  • 1Department of Sciences, John Jay College of Criminal Justice, City University of New York, New York, NY, 10019, USA. shcheng@jjay.cuny.edu.

Journal of Biochemical and Molecular Toxicology
|April 26, 2014
PubMed

Insights

This study reveals that pesticides Maneb (MB) and mancozeb (MZ) cause neurotoxicity by inducing DNA damage and activating the RTP801 and NF-κB pathways. These findings highlight a novel toxic mechanism for dithiocarbamate pesticides.

Area of Science:

  • Neuroscience
  • Toxicology
  • Environmental Health

Background:

  • Environmental factors, including pesticides like Maneb (MB) and mancozeb (MZ), are increasingly linked to neurodegenerative disease pathogenesis.
  • Previous research suggests MB can lower the threshold for dopaminergic damage and that MB/MZ potentiate MPP(+)-induced cytotoxicity via NF-κB activation.

Purpose of the Study:

  • To elucidate the toxic mechanisms of Maneb (MB) and mancozeb (MZ) in neuronal cells.
  • To investigate the role of RTP801 and its interaction with NF-κB in pesticide-induced neurotoxicity.

Main Methods:

  • Utilized comet assay to detect DNA damage induced by MB and MZ.
  • Assessed the expression of RTP801 protein and mRNA following MB and MZ exposure.
  • Employed shRNA to knock down RTP801 and analyzed its effect on NF-κB activation and cell death.

Main Results:

  • MB and MZ exposure induced significant DNA damage.
  • RTP801 protein and mRNA expression were elevated post-exposure to MB and MZ.
  • Knockdown of RTP801 demonstrated its regulatory role in MB/MZ-induced NF-κB activation and cell death.

Conclusions:

  • Dithiocarbamate pesticides MB and MZ induce neurotoxicity through DNA damage.
  • The toxic mechanism involves a crosstalk between RTP801 and NF-κB signaling pathways.
  • RTP801 plays a critical role in mediating cell death triggered by these pesticides.
Keywords:
NF-κBRTP801mancozebmaneb

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