Sphingolipids and cell differentiation

From LipidomicsWiki

S1P released from activated platelets that adhere to sites of damage is able to stimulate the migration of endothelial cells to the place of wound, where they attach and proliferate in response to S1P (Siess 2002). This effect is mediated by the activation of S1P1 receptor coupling to Gi protein and S1P3 coupling to several G proteins (Figure 37). Experimental data from HL-60 leukemia cells demonstrate that treatment of these cells with C2-ceramide or other ceramide analogs leads to cell differentiation confirming that exogenous application of short chain ceramide mimicks the action of TNFα, γ-interferon, 1α,25-dihydroxyvitamin D3 on HL-60 cells. Also studies carried out in neuronal cell lines confirmed that ceramide mimicks the effect of nerve growth factor on cell growth inhibition in T9 glioma cells (Dobrowsky et al. 1994). Ceramide is known to induce cell cycle arrest through dephosphorylation of the retinoblastoma gene product (Rb) in Molt-4 leukemia cells (Dbaibo et al. 1995). Experiments in yeast demonstrated that addition of exogenous ceramide to yeast Saccharomyces causes an antiproliferative response, resulting in arrest of cells in the G1 phase of the cell cycle (Nickels and Broach, 1996). Genetic analysis suggests that the ceramide effect on cell cycle arrest is partially mediated by ceramide-activated protein phosphatase as yeast strains carrying mutations in any of the genes coding for CAPP subunits are resistant to ceramide action.


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