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

Research output: Chapter in Book/Report/Conference proceedingConference contribution

1 Citation (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.

Original languageEnglish
Title of host publicationI International Symposium on Saffron Biology and Biotechnology
PublisherInternational Society for Horticultural Science
Number of pages12
ISBN (Print)9789066056770
Publication statusPublished - May 31 2004

Publication series

NameActa Horticulturae
ISSN (Print)0567-7572

All Science Journal Classification (ASJC) codes

  • Horticulture


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