TY - JOUR
T1 - Involvement of reactive oxygen species and stress-activated MAPKs in satratoxin H-induced apoptosis
AU - Nusuetrong, Punnee
AU - Yoshida, Makoto
AU - Tanitsu, Masa Aki
AU - Kikuchi, Haruhisa
AU - Mizugaki, Michinao
AU - Shimazu, Ken Ichi
AU - Pengsuparp, Thitima
AU - Meksuriyen, Duangdeun
AU - Oshima, Yoshiteru
AU - Nakahata, Norimichi
N1 - Funding Information:
This work was supported by Grants in PhD Program in Biopharmaceutical Sciences, Chulalongkorn University, Bangkok, Thailand, from Ministry of University Affairs of Thailand, and by Grants-in-Aid for Scientific Research 14572049 (to M.Y.) and 14370737 (to N.N.) from Japan Society for the Promotion of Science.
PY - 2005/1/10
Y1 - 2005/1/10
N2 - 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.
AB - 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.
KW - Apoptosis
KW - Glutathione
KW - Mitogen-activated protein kinase
KW - N-Acetyl-l-cysteine
KW - Reactive oxygen species
KW - Satratoxin H
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U2 - 10.1016/j.ejphar.2004.11.046
DO - 10.1016/j.ejphar.2004.11.046
M3 - Article
C2 - 15659314
AN - SCOPUS:19944431322
SN - 0014-2999
VL - 507
SP - 239
EP - 246
JO - European journal of pharmacology
JF - European journal of pharmacology
IS - 1-3
ER -