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This Article Full Text Full Text (PDF) All Versions of this Article: 294/1/C36    most recent 00164.2007v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Zanin, M. Articles by Danieli-Betto, D. Search for Related Content PubMed PubMed Citation Articles by Zanin, M. Articles by Danieli-Betto, D.

MUSCLE CELL BIOLOGY AND CELL MOTILITY

Trophic action of sphingosine 1-phosphate in denervated rat soleus muscle

¹Department of Human Anatomy and Physiology, University of Padua, Padua; ²Interuniversity Institute of Myology of Italy, ³Muscle Biology and Physiopathology Unit, Consiglio Nazionale delle Ricerche Institute of Neuroscience, Padua; ⁴Department of Biomedical Sciences University of Padua, Padua, Italy; and ⁵Department of Biology and Heart Institute, San Diego State University, San Diego, California

Submitted 17 April 2007 ; accepted in final form 10 October 2007

Sphingosine 1-phosphate (S1P) mediates a number of cellular responses, including growth and proliferation. Skeletal muscle possesses the full enzymatic machinery to generate S1P and expresses the transcripts of S1P receptors. The aim of this work was to localize S1P receptors in rat skeletal muscle and to investigate whether S1P exerts a trophic action on muscle fibers. RT-PCR and Western blot analyses demonstrated the expression of S1P₁ and S1P₃ receptors by soleus muscle. Immunofluorescence revealed that S1P₁ and S1P₃ receptors are localized at the cell membrane of muscle fibers and in the T-tubule membranes. The receptors also decorate the nuclear membrane. S1P₁ receptors were also present at the neuromuscular junction. The possible trophic action of S1P was investigated by utilizing the denervation atrophy model. Rat soleus muscle was analyzed 7 and 14 days after motor nerve cut. During denervation, S1P was continuously delivered to the muscle through a mini osmotic pump. S1P and its precursor, sphingosine (Sph), significantly attenuated the progress of denervation-induced muscle atrophy. The trophic effect of Sph was prevented by N,N-dimethylsphingosine, an inhibitor of Sph kinase, the enzyme that converts Sph into S1P. Neutralization of circulating S1P by a specific antibody further demonstrated that S1P was responsible for the trophic effects of S1P during denervation atrophy. Denervation produced the down regulation of S1P₁ and S1P₃ receptors, regardless of the presence of the receptor agonist. In conclusion, the results suggest that S1P acts as a trophic factor of skeletal muscle.

sphingosine 1-phosphate receptors; sphingomyelin derivatives; skeletal muscle atrophy