論文 - 詳細
| RRC ID | 43997 |
|---|---|
| 著者 | Nusuetrong P, Saito M, Kikuchi H, Oshima Y, Moriya T, Nakahata N. |
| タイトル | Apoptotic effects of satratoxin H is mediated through DNA double-stranded break in PC12 cells. |
| ジャーナル | J Toxicol Sci |
| 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. |
| 巻・号 | 37(4) |
| ページ | 803-12 |
| 公開日 | 2012-1-1 |
| DOI | 10.2131/jts.37.803 |
| PII | DN/JST.JSTAGE/jts/37.803 |
| PMID | 22863859 |
| MeSH | Animals Anthracenes / metabolism Apoptosis / drug effects* Blotting, Western Caspase 3 / genetics Caspase 3 / metabolism Comet Assay DNA Breaks, Double-Stranded / drug effects* DNA Damage / drug effects JNK Mitogen-Activated Protein Kinases / antagonists & inhibitors JNK Mitogen-Activated Protein Kinases / metabolism PC12 Cells Phosphorylation Poly (ADP-Ribose) Polymerase-1 Poly(ADP-ribose) Polymerases / genetics Poly(ADP-ribose) Polymerases / metabolism Rats Trichothecenes / toxicity* bcl-2-Associated X Protein / genetics bcl-2-Associated X Protein / metabolism p38 Mitogen-Activated Protein Kinases / genetics p38 Mitogen-Activated Protein Kinases / metabolism |
| IF | 1.737 |
| 引用数 | 4 |
| WOS 分野 | TOXICOLOGY |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 各媒体での言及数の合計 | 0 |
| リソース情報 | |
| ヒト・動物細胞 | PC-12(RCB0009) |