ABSTRACT
Satratoxin H, a mycotoxin, is thought to induce apoptosis of PC12 cells through the activation of p38 mitogen-activated protein kinase (MAPK) and c-Jun N-terminal kinase (JNK) in a glutathione (GSH)-sensitive manner. The present study was undertaken to further elucidate the mechanism by which satratoxin H induces cell death in PC12 cells. Satratoxin H caused apoptosis of PC12 cells within 24-h, as determined by DNA fragmentation and flow cytometric analysis. Satratoxin H increased reactive oxygen species (ROS) production and lipid peroxidation, as determined by malondialdehyde formation. These effects were attenuated by incubation of cells with GSH, suggesting that satratoxin H-induced increase in apoptosis of serum-deprived PC12 cells may be partially mediated through the generation of ROS.
Subject(s)
Lipid Peroxidation/drug effects , Reactive Oxygen Species/metabolism , Trichothecenes/toxicity , Animals , Antioxidants/pharmacology , Cell Survival/drug effects , DNA Fragmentation/drug effects , Electrophoresis, Agar Gel , Flow Cytometry , G1 Phase/drug effects , Glutathione/pharmacology , Indicators and Reagents , JNK Mitogen-Activated Protein Kinases/metabolism , PC12 Cells , Rats , Thiobarbituric Acid Reactive Substances/metabolism , Trichothecenes/antagonists & inhibitors , p38 Mitogen-Activated Protein Kinases/metabolismABSTRACT
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.
Subject(s)
Apoptosis/drug effects , Mitogen-Activated Protein Kinases/metabolism , Reactive Oxygen Species/metabolism , Stress, Physiological/metabolism , Trichothecenes/toxicity , Animals , Apoptosis/physiology , Cell Survival/drug effects , Cell Survival/physiology , Dose-Response Relationship, Drug , Mycotoxins/isolation & purification , Mycotoxins/pharmacology , Mycotoxins/toxicity , PC12 Cells , Rats , Trichothecenes/isolation & purification , Trichothecenes/pharmacologyABSTRACT
Two guaiane-type compounds, nardoguaianone J and K (1 and 2) and two aristolane-type compounds, kanshone F and G (3 and 4), were isolated from Nardostachys chinensis roots. The structures including the absolute configurations were elucidated by spectral means and by comparison of their CD spectra.
