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

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)