Present work was aimed at studying the effects of sphingosine-1 phosphate (S1P), a natural sphingomyelin derivative, on the trophism of slow-twitch skeletal muscle. The action of S1P was investigated during muscle denervation, an experimental model characterized by a marked reduction of muscle mass. First, we examined the possible trophic action of S1P by reducing the level of the circulating lipid by treating denervated mice with an antibody specific for S1P (three doses of 10 ìg/g of body weight injected intra-peritoneum). Denervation was performed by cutting monolaterally the sciatic nerve. The effect S1P removal was evaluated on muscle mass and fiber CSA. After 7 days, atrophy was significantly higher in animals without circulating S1P with respect to untreated animals. The action of S1P was also investigated by the exogenous supplementation of the lipid. In this case, denervation was performed in adult rats by the bilateral cutting of the sciatic nerve at the level of trochanter. Sphingosine (SPH, a precursor of S1P) or S1P were continuously released over soleus muscle by a mini-osmotic pump implanted subcutaneously in the scapular region and connected through a catheter to the muscle of the left leg. In general, both lipids decreased the development of atrophy in 7 and 14-day denervated soleus muscles, with SPH being the most effective. To verify the presence of S1P specific receptors at muscle fiber surface, the expression of S1P1 receptor and SCaMPER was investigated. The localization of these two receptors was demonstrated, for the first time, by immunofluorescence and western blot analyses, both in control and denervated skeletal muscles. Interestingly, the expression level of the receptors appears to be reduced during denervation. Present data seem to indicate that S1P signaling has trophic functions in skeletal muscle.

Sphingolipid signaling in denervated skeletal muscle

GERMINARIO, ELENA;DANIELI, DANIELA
2005

Abstract

Present work was aimed at studying the effects of sphingosine-1 phosphate (S1P), a natural sphingomyelin derivative, on the trophism of slow-twitch skeletal muscle. The action of S1P was investigated during muscle denervation, an experimental model characterized by a marked reduction of muscle mass. First, we examined the possible trophic action of S1P by reducing the level of the circulating lipid by treating denervated mice with an antibody specific for S1P (three doses of 10 ìg/g of body weight injected intra-peritoneum). Denervation was performed by cutting monolaterally the sciatic nerve. The effect S1P removal was evaluated on muscle mass and fiber CSA. After 7 days, atrophy was significantly higher in animals without circulating S1P with respect to untreated animals. The action of S1P was also investigated by the exogenous supplementation of the lipid. In this case, denervation was performed in adult rats by the bilateral cutting of the sciatic nerve at the level of trochanter. Sphingosine (SPH, a precursor of S1P) or S1P were continuously released over soleus muscle by a mini-osmotic pump implanted subcutaneously in the scapular region and connected through a catheter to the muscle of the left leg. In general, both lipids decreased the development of atrophy in 7 and 14-day denervated soleus muscles, with SPH being the most effective. To verify the presence of S1P specific receptors at muscle fiber surface, the expression of S1P1 receptor and SCaMPER was investigated. The localization of these two receptors was demonstrated, for the first time, by immunofluorescence and western blot analyses, both in control and denervated skeletal muscles. Interestingly, the expression level of the receptors appears to be reduced during denervation. Present data seem to indicate that S1P signaling has trophic functions in skeletal muscle.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11577/1422504
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