Articles
PREVENTION OF PC-12 CELL DEATH BY CROCIN VIA SPHINGOMYELINASE-CERAMIDE SIGNALING BY INCREASE OF GLUTATHIONE BIOSYNTHESIS
Article number
650_53
Pages
423 – 434
Language
English
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.
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.
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
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