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1 Kinesiology, University of Illinois, Chicago, Chicago, IL, USA
2 Applied Physiology, Georgia Institute of Technology, Atlanta, GA, USA
* To whom correspondence should be addressed. E-mail: karyn.esser{at}uky.edu.
Several lines of evidence suggest that muscle cells can distinguish between specific mechanical stimuli. To test this concept, C2C12 myotubes were subjected to cyclic uniaxial or multiaxial stretch. Both types of stretch induced an increase in extracellular-regulated kinase (ERK) and protein kinase B (PKB/Akt) phosphorylation, but only multiaxial stretch induced ribosomal S6 kinase (p70S6k) phosphorylation. Further results demonstrated that the signaling events specific to multiaxial stretch (p70S6k phosphorylation) were elicited by forces delivered through the elastic culture membrane and were not due to greater surface area deformations, or localized regions of large tensile strain. Experiments using media that was conditioned by multiaxial stretched myotubes indicated that a release of paracrine factors was not sufficient for the induction of signaling to p70S6k. Furthermore, incubation with Gadolinium(III) chloride (500µM), Genistein (250µM), PD98059 (250µM), Bisindolylmaleimide I (20µM) and LY294002 (100µM ) did not block the multiaxial stretch induced signaling to p70S6k. However, disrupting the actin cytoskeleton with Cytochalasin D did block the multiaxial signaling to p70S6k, with no effect on signaling to PKB/Akt. These results demonstrate that specific types of mechanical stretch activate distinct signaling pathways and we propose that this occurs through direct mechanosensory-mechanotransduction mechanisms and not through previously defined growth factor/receptor binding pathways.
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