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II. ABSTRACT
II. ABSTRACT
II. ABSTRACT
II. ABSTRACT
Sphingolipids, besides being components of eukaryotes membranes, play an important role as regulators of various cellular processes such as proliferation, growth, migration, differentiation, ageing and apoptosis.
The intracellular effects of sphingolipid metabolites depend on the stage of cellular development as well as on the specific sub-compartment in which they are produced. It is believed that the relative intracellular level of the different sphingolipid metabolites, rather than their absolute amount, is the critical factor to determine the cellular fate. This has led many researchers to propose the so-called "rheostat " model. According to this model, for instance, the ratio between intracellular ceramide and S1P would be crucial in determining whether a cell dyes or survives.
The aim of this work has been to assess the mitogenic action of two sphingolipid metabolites, the Sphingosine-1-phosphate (S1P) and the Sphingosylphosphorylcholine (SPC), on the cell line HN9.10e produced by somatic cell fusion of hippocampal cells and cells neuroblastoma from mouse.
The changes determined by these two sphingolipids in the free Ca2+ content of endoplasmic reticulum has been also measured, and, in particular, it has been studied the location and the role of a new calcium channel, called SCaMPER, identified on the ER whose activation seems to be mediated by sphingolipids.
Our experiments have shown that low concentrations of S1P and SPC have a mitogenic effect on HN9.10e cell line inducing release of calcium from ER. We have also shown that SCaMPER is involved in the calcium signalling induced by S1P and SPC.
