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)

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 - May 31 2004

Publication series

NameActa Horticulturae
Volume650
ISSN (Print)0567-7572

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ceramides
cell death
glutathione
biosynthesis
phosphotransferases (kinases)
cells
phosphorylation
Crocus sativus
saffron
glucose
tumor necrosis factors
glycosides
magnesium
medicine
apoptosis
neurons
synthesis

All Science Journal Classification (ASJC) codes

  • Horticulture

Cite this

Ochiai, T., Soeda, S., Ohno, S., Shimeno, H., Tanaka, H., Shoyama, Y., ... 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

Prevention of PC-12 cell death by crocin via sphingomyelinase-ceramide signaling by increase of glutathione biosynthesis. / Ochiai, Takashi; Soeda, Shinji; Ohno, Shigekazu; Shimeno, Hiroshi; Tanaka, Hiroyuki; Shoyama, Yukihiro; Molnar, Joseph; Berek, Livia; Bartok, Tibor.

I International Symposium on Saffron Biology and Biotechnology. International Society for Horticultural Science, 2004. p. 423-434 (Acta Horticulturae; Vol. 650).

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

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. Acta Horticulturae, vol. 650, International Society for Horticultural Science, pp. 423-434. https://doi.org/10.17660/ActaHortic.2004.650.53
Ochiai T, Soeda S, Ohno S, Shimeno H, Tanaka H, Shoyama Y et al. 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. International Society for Horticultural Science. 2004. p. 423-434. (Acta Horticulturae). https://doi.org/10.17660/ActaHortic.2004.650.53
Ochiai, Takashi ; Soeda, Shinji ; Ohno, Shigekazu ; Shimeno, Hiroshi ; Tanaka, Hiroyuki ; Shoyama, Yukihiro ; Molnar, Joseph ; Berek, Livia ; Bartok, Tibor. / Prevention of PC-12 cell death by crocin via sphingomyelinase-ceramide signaling by increase of glutathione biosynthesis. I International Symposium on Saffron Biology and Biotechnology. International Society for Horticultural Science, 2004. pp. 423-434 (Acta Horticulturae).
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