Apoptotic effects of satratoxin H is mediated through DNA double-stranded break in PC12 cells

Punnee Nusuetrong1, Masaki Saito, Haruhisa Kikuchi

  • 1Department of Cellular Signaling, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Japan.

Insights

Satratoxin H, a mycotoxin, triggers apoptosis and DNA damage in PC12 cells via caspase-3 and PARP pathway activation. It induces genotoxicity through DNA double-strand breaks, posing a health risk.

Area of Science:

  • Toxicology
  • Molecular Biology
  • Cell Biology

Background:

  • Satratoxin H is an air- and food-borne mycotoxin linked to human health issues.
  • It is known to induce apoptosis and genotoxicity in PC12 cells.

Purpose of the Study:

  • Investigate the mechanism of satratoxin H-induced apoptosis, focusing on the caspase-3 and poly-ADP-ribose polymerase (PARP) pathway.
  • Examine satratoxin H's genotoxicity in PC12 cells, specifically DNA damage induction.

Main Methods:

  • PC12 cells were treated with satratoxin H.
  • Caspase-3 and PARP cleavage were assessed.
  • p38 MAPK and JNK inhibitors (SB203580, SP600125) were used.
  • Bax and Bcl-2 expression levels were analyzed.
  • Micronucleus and alkaline comet assays were performed.
  • Histone H2A phosphorylation was measured.

Main Results:

  • Satratoxin H induced time-dependent cleavage of caspase-3 and PARP.
  • Inhibitors of p38 MAPK and JNK partially blocked this cleavage.
  • No significant changes in Bax and Bcl-2 expression were observed.
  • Micronucleus assay indicated chromosome breaks.
  • Histone H2A phosphorylation confirmed DNA double-strand breaks.
  • Alkaline comet assay did not detect genotoxicity.

Conclusions:

  • Satratoxin H induces genotoxicity primarily through DNA double-strand breaks.
  • The caspase-3/PARP pathway is involved in satratoxin H-induced apoptosis.
  • SB203580 and SP600125 can inhibit satratoxin H-induced apoptosis.
  • Satratoxin H presents a significant genotoxic risk.

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