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- Title
Apoptotic effects of satratoxin H is mediated through DNA double-stranded break in PC12 cells.
- Authors
Punnee Nusuetrong; Masaki Saito; Haruhisa Kikuchi; Yoshiteru Oshima; Takahiro Moriya; Norimichi Nakahata
- 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.
- Subjects
APOPTOSIS; GENETIC toxicology; TRICHOTHECENES; DNA damage; MYCOTOXINS; FOODBORNE diseases; CASPASES; POLY ADP ribose
- Publication
Journal of Toxicological Sciences, 2012, Vol 37, Issue 4, p803
- ISSN
0388-1350
- Publication type
Article
- DOI
10.2131/jts.37.803