Quercetin Affects Ceramide but not Sphingosine-1-phosphate in ras-transformed 3T3 Fibroblasts

Implication of Ceramide, Ceramide 1-Phosphate and Sphingosine 1-Phosphate in Tumorigenesis

In the last two decades there has been considerable progress in our understanding of the role of sphingolipids in controlling signal transduction processes, particularly in the mechanisms leading to regulation of cell growth and death. Ceramide is a well-characterized sphingolipid metabolite and second messenger that can be produced by cancer cells in response to a variety of stimuli, including...

Spry2 does not directly modulate Raf-1 kinase activity in v-Ha-ras-transformed NIH 3T3 fibroblasts.

Sprouty (Spry) proteins have previously been suggested as negative regulators of the MAPK pathway through interaction with Raf-1. However, the molecular basis of this inhibition has not been elucidated. In this study, we used cells expressing FLAGtagged Raf-1 with point mutations at known phosphorylation sites to reveal that activation of Raf-1 mutants does not correlate with their degree of in...

Phosphorylated cis-4-methylsphingosine mimics the mitogenic effect of sphingosine-1-phosphate in Swiss 3T3 fibroblasts.

The phosphorylated derivative of sphingosine, sphingosine-1-phosphate, is a short-living metabolite of ultimate ceramide degradation and was shown to act as an intracellular signaling molecule, stimulating cell proliferation in quiescent Swiss 3T3 fibroblasts and inducing the release of calcium from intracellular stores (Zhang, H., Desai, N. N., Olivera, A., Seki, T., Brooker, G., and Spiegel, ...

Energy balance and the sphingosine-1-phosphate/ceramide axis

Sphingosine-1-phosphate protects proliferating endothelial cells from ceramide-induced apoptosis but not from DNA damage-induced mitotic death.

Because of the central role of the endothelium in tissue homeostasis, protecting the vasculature from radiation-induced death is a major concern in tissue radioprotection. Premitotic apoptosis and mitotic death are two prevalent cell death pathways induced by ionizing radiation. Endothelial cells undergo apoptosis after radiation through generation of the sphingolipid ceramide. However, if mito...