Zanin, Marika (2008) Identificazione dei recettori specifici per S1P nel muscolo soleo di ratto. Ruolo dei derivati della sfingomielina sul trofismo del muscolo scheletrico. [Ph.D. thesis]
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S1P is a bioactive metabolite of Sphingomyelin implicated in many biological processes, including growth and proliferation. This molecule can function intracellularly, as a second messenger, or extracellularly, activating S1P receptors present on the cell surface. Skeletal muscle express all the enzymes that compose the Sphingomyelin pathway, that create sphingolipids as demonstrated by the high levels in the T tubular system of Sphyngomyielin and Sphingosine (Sph, precursor of S1P) and by a great activity of sphingomyelinase, that catalyses the first step in the pathway. The sphingolipid derivates are also present at high concentration on blood, and thus skeletal muscle is steadily controlled by these factors. The first part of this research aimed to study the expression and the localization of S1P receptors in rat skeletal muscle. RT-PCR and Western Blot analyses demonstrated the expression of S1P1 and S1P3 receptors in adult soleus muscle. Immunofluorescence revealed that both S1P1 and S1P3 receptors are localized at the cell membrane of muscle fibers and in the T-tubule membranes, but only S1P1 receptor is present at higher expression at the neuromuscular junction. Both the receptors have been found also to decorate the nuclear membrane and to be expressed in the satellite cells. As the presence of S1P1 and S1P3 on skeletal muscle seemed to suggest a possible physiological action of S1P, thus the second part of the research aimed to investigate the possibility that S1P acts as trophic factor. It was studied the action of S1P and Sph by means of the model of atrophy induced by the denervation and the model of in vivo regeneration.
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