Involvement of reactive oxygen species and stress-activated MAPKs in satratoxin H-induced apoptosis.
Satratoxins, members of the trichothecene mycotoxin family, have been known to be harmful to health. However, the mechanisms underlying the toxicity still remain unclear. The present study is undertaken to elucidate the mechanisms of the satratoxin H-induced cytotoxicity in PC12 cells. Satratoxin H caused cytotoxicity, which was reflected from apoptosis determined by chromatin staining and flow cytometry. Satratoxin H stimulated the phosphorylation of extracellular signal-regulated kinase (ERK), p38 mitogen-activated protein kinase (MAPK) and c-Jun N-terminal kinase (JNK). Pre-incubation with SB203580, a p38 MAPK inhibitor, or SP600125, a JNK inhibitor, but not PD98059, an ERK inhibitor, reduced satratoxin-induced cytotoxicity. Co-incubation of cells with glutathione, N-acetyl-L-cysteine or glutathione reductase inhibited cytotoxicity and the phosphorylation of p38 MAPK induced by satratoxin H. Our data suggest that satratoxin H-induced apoptosis in PC12 cells is dependent on the activation of p38 MAPK/JNK and the increase in reactive oxygen species.
Nusuetrong
Punnee
P
Department of Cellular Signaling, Graduate School of Pharmaceutical Sciences, Tohoku University, 6-3 Aoba, Aramaki, Aoba-ku, Sendai 980-8578, Japan.
Yoshida
Makoto
M
Tanitsu
Masa-aki
MA
Kikuchi
Haruhisa
H
Mizugaki
Michinao
M
Shimazu
Ken-ichi
K
Pengsuparp
Thitima
T
Meksuriyen
Duangdeun
D
Oshima
Yoshiteru
Y
Nakahata
Norimichi
N
D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D009183:Mycotoxins / Q000302:isolation & purification / Q000494:pharmacology / Q000633:toxicity; D016716:PC12 Cells; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013312:Stress, Physiological / Q000378:metabolism*; D014255:Trichothecenes / Q000302:isolation & purification / Q000494:pharmacology / Q000633:toxicity*
D009183:Mycotoxins; D017382:Reactive Oxygen Species; D014255:Trichothecenes; C014184:satratoxin H; D020928:Mitogen-Activated Protein Kinases