Prevention of PC-12 cell death by crocin via sphingomyelinase-ceramide signaling by increase of glutathione biosynthesis

Takashi Ochiai, Shinji Soeda, Shigekazu Ohno, Hiroshi Shimeno, Hiroyuki Tanaka, Yukihiro Shoyama, Joseph Molnar, Livia Berek, Tibor Bartok

研究成果: Chapter in Book/Report/Conference proceedingConference contribution

1 被引用数 (Scopus)


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-α. 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/glucosedeprived 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 (γ-GCS), contributing to a stable GSH supply that blocks the activation of N-SMase. Thus our data suggest that crocin combats the serum/glucose deprivationinduced 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.

ホスト出版物のタイトルI International Symposium on Saffron Biology and Biotechnology
出版社International Society for Horticultural Science
出版ステータス出版済み - 5 31 2004


名前Acta Horticulturae

All Science Journal Classification (ASJC) codes

  • 園芸学


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