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Sphingosine-induced c-jun expression: differences between sphingosine- and C2-ceramide-mediated signaling pathways
Hirofumi Sawai1, Toshiro Okazaki, Naochika Domae
1Department of Internal Medicine, Osaka Dental University, 8-1 Kuzuhahanazono-cho, Hirakata, Osaka, Japan. sawai@cc.osaka-dent.ac.jp
FEBS Letters
|July 24, 2002
Summary
Sphingolipids like ceramide and sphingosine induce c-jun expression and apoptosis in leukemia cells. However, they utilize distinct signaling pathways, with sphingosine
Area of Science:
- Cellular biology
- Biochemistry
- Molecular signaling
Background:
- Sphingolipids, including ceramide and sphingosine, are key intracellular mediators involved in critical cellular processes such as differentiation, growth inhibition, and apoptosis.
- Previous research demonstrated that C2-ceramide induces c-jun expression during apoptosis in human leukemia HL-60 cells.
Purpose of the Study:
- To investigate the role of sphingosine in c-jun expression and apoptosis in HL-60 cells.
- To elucidate the distinct signaling pathways utilized by sphingosine and C2-ceramide in inducing c-jun expression and apoptosis.
Main Methods:
- Utilized human leukemia HL-60 cell line.
- Administered sphingosine and C2-ceramide.
- Employed H-89 (protein kinase A inhibitor) and protein kinase C inhibitors.
- Monitored c-jun expression and cell growth inhibition.
Main Results:
- Sphingosine, similar to C2-ceramide, induced c-jun expression in HL-60 cell apoptosis.
- Sphingosine-induced c-jun expression was enhanced by H-89, while C2-ceramide-induced c-jun expression was inhibited by protein kinase C inhibitors.
- H-89 potentiated sphingosine-induced growth inhibition but not C2-ceramide-induced growth inhibition.
Conclusions:
- Sphingosine and C2-ceramide activate distinct signaling pathways to induce c-jun expression and apoptosis.
- Protein kinase A and C signaling pathways play differential roles in mediating the effects of sphingosine and C2-ceramide, respectively.