ISHS Acta Horticulturae 650: I International Symposium on Saffron Biology and Biotechnology
PREVENTION OF PC-12 CELL DEATH BY CROCIN VIA SPHINGOMYELINASE-CERAMIDE SIGNALING BY INCREASE OF GLUTATHIONE BIOSYNTHESIS |
| Authors: | T. Ochiai, S. Soeda, S. Ohno, H. Shimeno, H. Tanaka, Y. Shoyama, J. Molnar, L. Berek, T. Bartok |
| Keywords: | Crocus sativus L., Iridaceae, glutathione increase |
| DOI: | 10.17660/ActaHortic.2004.650.53 |
| Abstract:
Crocetin glycoside, crocin is a pharmacologically active component of Crocus sativus L. (saffron) that has been used in traditional Chinese medicine. Previously we demonstrated that crocin inhibited apoptosis in PC-I2 cells by affecting the function of tumor necrosis factor-  . In this study, we found that depriving cultured PC-12 cells of serum/glucose causes a rapid increase in cellular ceramide levels, followed by an increase in the phosphorylation of c-jun kinase (JNK). The accumulation of ceramide was found to depend on the activation of magnesium-dependent neutral sphingomyelinase (N-SMase), but not on de novo synthesis.
The serum/glucose-deprived PC-12 cells also decreased the cellular levels of glutathione (GSH), which is the potent inhibitor of N-SMase.
Treating the PC-12 cells with crocin prevented N-SMase activation, ceramide production, and JNK phosphorylation.
We also found that the chemical can enhance the activities of GSH reductase and glutamylcysteinyl synthase ( -GCS), contributing to a stable GSH supply that blocks the activation of N-SMase.
Thus our data suggest that crocin combats the serum/glucose deprivation-induced ceramide formation in PC-12 cells by increasing GSH levels and prevents the activation of JNK pathway, which is reported to have a role of the signaling cascade downstream ceramide for neuronal cell death.
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