Apoptotic effects of satratoxin H is mediated through DNA double-stranded break in PC12 cells
Punnee Nusuetrong1, Masaki Saito, Haruhisa Kikuchi
1Department of Cellular Signaling, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Japan.
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.
Insights
Satratoxin H, a mycotoxin, triggers apoptosis and DNA damage in PC12 cells via caspase-3 and PARP pathway activation. It induces genotoxicity through DNA double-strand breaks, posing a health risk.
Area of Science:
- Toxicology
- Molecular Biology
- Cell Biology
Background:
- Satratoxin H is an air- and food-borne mycotoxin linked to human health issues.
- It is known to induce apoptosis and genotoxicity in PC12 cells.
Purpose of the Study:
- Investigate the mechanism of satratoxin H-induced apoptosis, focusing on the caspase-3 and poly-ADP-ribose polymerase (PARP) pathway.
- Examine satratoxin H's genotoxicity in PC12 cells, specifically DNA damage induction.
Main Methods:
- PC12 cells were treated with satratoxin H.
- Caspase-3 and PARP cleavage were assessed.
- p38 MAPK and JNK inhibitors (SB203580, SP600125) were used.
- Bax and Bcl-2 expression levels were analyzed.
- Micronucleus and alkaline comet assays were performed.
- Histone H2A phosphorylation was measured.
Main Results:
- Satratoxin H induced time-dependent cleavage of caspase-3 and PARP.
- Inhibitors of p38 MAPK and JNK partially blocked this cleavage.
- No significant changes in Bax and Bcl-2 expression were observed.
- Micronucleus assay indicated chromosome breaks.
- Histone H2A phosphorylation confirmed DNA double-strand breaks.
- Alkaline comet assay did not detect genotoxicity.
Conclusions:
- Satratoxin H induces genotoxicity primarily through DNA double-strand breaks.
- The caspase-3/PARP pathway is involved in satratoxin H-induced apoptosis.
- SB203580 and SP600125 can inhibit satratoxin H-induced apoptosis.
- Satratoxin H presents a significant genotoxic risk.
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