Molecular and Biomechanical Adaptations to Mechanical Stretch in Cultured Myotubes

Figures

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  Figure 1. Stretch-released growth factors and prostaglandins regulated protein synthesis of myotubes. Stretch activated G protein-coupled receptors, such as calcium influx channels and IGF-1 receptors, in the membrane of myotubes, leading to elevated activities of phospholipases (PLA, PLD) and PG endoperoxide GH synthase (PGHS). PLA and PLD liberated arachidonic acid, which was subsequently converted by PGHS into prostaglandins production, such as PGE2 and PGF2. On the other hand, stretching stimuli could also promote growth factors (IGF1 and FGF) that participated in myotube protein synthesis through binding to their specific receptors. Whether these two major mechanisms acted simultaneously to regulate anabolism of myotubes under stretching environment would be a matter of interest.

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  Figure 2. Pathways involving in stretch-induced myotube anabolism as well as their potential cross-talk. There were several pathways being proposed so far that mediate protein synthesis and myotube growth in stretching environment. Basically, stretching stimulated these pathways by distortion of myotube membrane, leading to activation of some membrane-residing proteins. Signaling molecules such as tyrosine kinases or phosphatase were involved in downward transmission, causing phosphorylation, or dephosphorylation of effector proteins (ERK, AKT, mTOR, p70S6K), and finally regulated the anabolism of myotubes.

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  Figure 3. Stretch-induced myotube cytoskeletal reconstruction and cellular damage. Cytoskeletal proteins such as sarcoglycan, plectin, as well as membrane caveolae protein caveolin-3 are all critical proteins that participated in myotube cytoskeleton adaptation to mechanical stretch by activating signalings such as p70S6K, STAT3, ERK. In addition, release of NO also played a role in activating PKG pathway. The activation of these pathways contributed to expressions of structure proteins desmin, talin and vinculin, which are beneficial to reconstructions of myotube cytoskeleton. On the other hand, deficiency of the sarcoglycan led to abnormal activities of Ca2+ and Na+ channels, which caused intracellular Ca2+ overloading and activation of Ca2+ dependent hydrolase, calpain, that promoted cytoskeletal protein proteolysis and cellular damage.

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  Figure 4. Stretch-regulated secretion of myotubes. When myotubes were stimulated by mechanical stretch, various kinds of cytokines were released out of myotubes and exerted distinct functions. Some of these cytokines acted in an autocrine fashion, regulating glucose uptake, protein synthesis, and cytoskeletal adaption of myotubes in response to mechanical stretch. In addition, there were other cytokines that were involved in cross-talk of stretched myotubes with other types of cells, such as neutrophil, motoneurons, osteoclasts, and endothelial cells.