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.
|
Authors | Punnee Nusuetrong, Masaki Saito, Haruhisa Kikuchi, Yoshiteru Oshima, Takahiro Moriya, Norimichi Nakahata |
Journal | The Journal of toxicological sciences
(J Toxicol Sci)
Vol. 37
Issue 4
Pg. 803-12
( 2012)
ISSN: 1880-3989 [Electronic] Japan |
PMID | 22863859
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
|
Chemical References |
- Anthracenes
- Trichothecenes
- bcl-2-Associated X Protein
- pyrazolanthrone
- satratoxin H
- Parp1 protein, rat
- Poly (ADP-Ribose) Polymerase-1
- Poly(ADP-ribose) Polymerases
- JNK Mitogen-Activated Protein Kinases
- p38 Mitogen-Activated Protein Kinases
- Casp3 protein, rat
- Caspase 3
|
Topics |
- Animals
- Anthracenes
(metabolism)
- Apoptosis
(drug effects)
- Blotting, Western
- Caspase 3
(genetics, metabolism)
- Comet Assay
- DNA Breaks, Double-Stranded
(drug effects)
- DNA Damage
(drug effects)
- JNK Mitogen-Activated Protein Kinases
(antagonists & inhibitors, metabolism)
- PC12 Cells
- Phosphorylation
- Poly (ADP-Ribose) Polymerase-1
- Poly(ADP-ribose) Polymerases
(genetics, metabolism)
- Rats
- Trichothecenes
(toxicity)
- bcl-2-Associated X Protein
(genetics, metabolism)
- p38 Mitogen-Activated Protein Kinases
(genetics, metabolism)
|