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

Punnee Nusuetrong, Masaki Saito, Haruhisa Kikuchi, Yoshiteru Oshima, Takahiro Moriya, Norimichi Nakahata

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Satratoxin H is an important air- and food-borne mycotoxin, which has been implicated in human health damage. Satratoxin H is known to induce apoptosis as well as genotoxicity in PC12 cells. In the present study, we further investigated the mechanism of apoptotic effects of satratoxin H with focus on caspase-3 and poly-ADP-ribose polymerase (PARP) pathway. We also examined whether it induces DNA damage in PC12 cells. In the cells treated with satratoxin H, caspase-3 was cleaved in a time-dependent manner. Furthermore, satratoxin H induced cleavage of PARP, one of the downstream molecules of caspase-3. The cleavage was inhibited by SB203580, a p38 MAPK inhibitor, or SP600125, a JNK inhibitor. Satratoxin H, however, had no effect on expression levels of Bax and Bcl-2. Furthermore, the micronucleus assay revealed that satratoxin H induced chromosome break. Also, satratoxin H increased the level of phosphorylation of histone H2A, indicating that it caused DNA double-stranded breaks in PC12 cells. Meanwhile, no genotoxicity was detected with any of treatments carried out in the alkaline comet assay. These results imply that satratoxin H induces genotoxicity by DNA double-stranded break. Our results suggest a considerable potential for the genotoxic risk associated with the presence of satratoxin H.

Original languageEnglish
Pages (from-to)803-812
Number of pages10
JournalJournal of Toxicological Sciences
Volume37
Issue number4
DOIs
Publication statusPublished - 2012

Keywords

  • Apoptosis
  • Caspase-3
  • DNA break
  • Satratoxin H
  • Stachybotrys atra

ASJC Scopus subject areas

  • Toxicology

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