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: Conference contribution

1 Citation (Scopus)

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-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
Pages423-434
Number of pages12
ISBN (Print)9789066056770
DOIs
Publication statusPublished - máj. 31 2004

Publication series

NameActa Horticulturae
Volume650
ISSN (Print)0567-7572

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ASJC Scopus subject areas

  • Horticulture

Cite this

Ochiai, T., Soeda, S., Ohno, S., Shimeno, H., Tanaka, H., Shoyama, Y., Molnar, J., Berek, L., & Bartok, T. (2004). Prevention of PC-12 cell death by crocin via sphingomyelinase-ceramide signaling by increase of glutathione biosynthesis. In I International Symposium on Saffron Biology and Biotechnology (pp. 423-434). (Acta Horticulturae; Vol. 650). International Society for Horticultural Science. https://doi.org/10.17660/ActaHortic.2004.650.53