Role of Sphingosine 1-Phosphate in Skeletal Muscle Cell Biology
Studies performed in the last fifteen years have clearly established that the bioactive sphingolipid sphingosine 1-phosphate (S1P) affects various different biological properties of myogenic precursor cells as well as physiological features of adult skele
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Contents 1 Skeletal Muscle Structure and Cell Biology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2 S1P in the Regulation of Growth, Differentiation and Motility of Skeletal Muscle Cells . . . 3 S1P in the Regulation of the Biology and Physiology of Skeletal Muscle . . . . . . . . . . . . . . . 4 Regulation of SK/S1P Axis by Growth Factors, Cytokines and Hormones in Myoblasts . . . References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
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Abstract Studies performed in the last fifteen years have clearly established that the bioactive sphingolipid sphingosine 1-phosphate (S1P) affects various different biological properties of myogenic precursor cells as well as physiological features of adult skeletal muscle. Noticeably, in myogenic precursor cells multiple growth factors and cytokines cross-communicate with S1P axis and the engagement of distinct S1P receptor subtypes appears to be crucially implicated in transmitting specific biological effects. This paper summarizes current research findings and discloses the potential for new therapeutics designed to alter S1P signaling with the aim of improving skeletal muscle repair. Keywords myoblasts • skeletal muscle • sphingosine 1-phosphate • sphingosine kinase • S1P receptor
P. Bruni (*) • C. Donati Dipartimento di Scienze Biochimiche, Sperimentali e Cliniche, Universita` di Firenze, Viale GB Morgagni 50, 50134 Firenze, Italy e-mail: [email protected] E. Gulbins and I. Petrache (eds.), Sphingolipids in Disease, Handbook of Experimental Pharmacology 216, DOI 10.1007/978-3-7091-1511-4_23, # Springer-Verlag Wien 2013
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1 Skeletal Muscle Structure and Cell Biology A little less than one-half of the body’s mass is composed of skeletal muscle, with most muscles linked to bones by tendons through which the forces and movements developed during contractions are transmitted to the skeleton. The smallest contractile unit of skeletal muscle is the muscle fibre or myofibre, which is a long cylindrical cell that contains many nuclei, mitochondria and sarcomeres. Contraction, defined as the activation of muscle fibres with a tendency of the fibres to shorten, occurs when an increase in the cytosolic calcium concentration triggers a series of molecular events that includes the binding of calcium to the muscleregulatory proteins, the interaction of myosin cross-bridges with actin filaments and the production of the cross-bridge working stroke. Skeletal muscles vary considerably in size, shape and arrangement of myofibres; moreover, they often contain a mixture of three distinct types of myofibres, which differ by the myosin isoforms expressed and the consequential contractile characteristics (Geeves and Holmes 1999). Type 1 myofibres are slow twitch and fatigue resistant, type 2A myofibres are fast twitch and moderately fatigue resistant and type 2B myo
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