Publication: Apoptotic effects of satratoxin H is mediated through DNA double-stranded break in PC12 cells
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Issued Date
2012
Resource Type
File Type
application/pdf
ISSN
18803989
Other identifier(s)
2-s2.0-84865636333
Rights Holder(s)
Scopus
Bibliographic Citation
Journal of Toxicological Sciences. Vol 37, No.4 (2012), p.803-812
Suggested Citation
Nusuetrong P., Saito M., Kikuchi H., Oshima Y., Moriya T., Nakahata N. Apoptotic effects of satratoxin H is mediated through DNA double-stranded break in PC12 cells. Journal of Toxicological Sciences. Vol 37, No.4 (2012), p.803-812. doi:10.2131/jts.37.803 Retrieved from: https://hdl.handle.net/20.500.14740/6974
Author(s)
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.
Subject(s)
4 (4 fluorophenyl) 2 (4 methylsulfinylphenyl) 5 (4 pyridyl)imidazole
Anthra[1,9 cd]pyrazol 6(2h) one
Caspase 3
Double stranded DNA
Histone H2A
Mycotoxin
Protein Bax
Protein bcl 2
Satratoxin h
Unclassified drug
Animal cell
Apoptosis
Article
Cell strain
Chromosome breakage
Controlled study
DNA strand breakage
Genotoxicity
Micronucleus test
Nonhuman
Protein blood level
Protein cleavage
Protein expression
Rat
Animals
Anthracenes
Apoptosis
Bcl-2-Associated X Protein
Blotting, Western
Caspase 3
Comet Assay
DNA Breaks, Double-Stranded
DNA Damage
JNK Mitogen-Activated Protein Kinases
P38 Mitogen-Activated Protein Kinases
PC12 Cells
Phosphorylation
Poly(ADP-ribose) Polymerases
Rats
Trichothecenes
Stachybotrys chartarum
Anthra[1,9 cd]pyrazol 6(2h) one
Caspase 3
Double stranded DNA
Histone H2A
Mycotoxin
Protein Bax
Protein bcl 2
Satratoxin h
Unclassified drug
Animal cell
Apoptosis
Article
Cell strain
Chromosome breakage
Controlled study
DNA strand breakage
Genotoxicity
Micronucleus test
Nonhuman
Protein blood level
Protein cleavage
Protein expression
Rat
Animals
Anthracenes
Apoptosis
Bcl-2-Associated X Protein
Blotting, Western
Caspase 3
Comet Assay
DNA Breaks, Double-Stranded
DNA Damage
JNK Mitogen-Activated Protein Kinases
P38 Mitogen-Activated Protein Kinases
PC12 Cells
Phosphorylation
Poly(ADP-ribose) Polymerases
Rats
Trichothecenes
Stachybotrys chartarum
