| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
B transcription factor
Department of Medicine, Baylor College of Medicine, Houston, Texas, USA
1Correspondence: Department of Medicine, Pulmonary and Critical Care Section, Suite 520B, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA. E-mail: axkumar{at}bcm.tmc.edu
Myogenesis is a multistep developmental program that generates and regenerates skeletal muscles. Several extracellular factors have been identified that participate in the regulation of myogenesis. Although skeletal muscles are always subjected to mechanical stress in vivo, the role of mechanical forces in the regulation of myogenesis remains unknown. We have investigated the molecular mechanisms by which cyclic mechanical strain modulates myogenesis. Application of cyclic mechanical strain using the computer-controlled Flexcell Strain Unit increased the proliferation of C2C12 cells and inhibited their differentiation into myotubes. Cyclic strain increased the activity of cyclin-dependent kinase 2 (cdk2) and the cellular level of cyclin A, and inhibited the expression of myosin heavy chain and formation of myotubes in C2C12 cultures. The activity of nuclear factor-kappa B (NF-
B) transcription factor and the expression of NF-B-regulated genes, cyclin D1 and IL-6, were augmented in response to mechanical strain. Cyclic strain also increased the activity of Rho GTPases, especially Rac-1. The inhibition of Rho GTPases activity, by overexpression of Rho GDP dissociation inhibitor (Rho-GDI), inhibited the strain-induced activation of NF-B in C2C12 cells. Overexpression of either NF-B inhibitory protein IB
N (a degradation resistant mutant IB) or Rho-GDI blocked the strain-induced proliferation of C2C12 cells. Furthermore, overexpression of FRNK, a dominant negative mutant of focal adhesion kinase (FAK), inhibited the strain-induced proliferation of C2C12 cells. Our study demonstrates that cyclic mechanical strain inhibits myogenesis through the activation of FAK, Rac-1, and NF-B.—Kumar, A., Murphy, R., Robinson, P., Wei, L., Boriek, A. M. Cyclic mechanical strain inhibits skeletal myogenesis through activation of focal adhesion kinase, Rac-1 GTPase, and NF-B transcription factor.
Key Words: skeletal myogenesis • C2C12 cells • cyclic stretch • FAK • Rac-1 • NF-kappa B
This article has been cited by other articles:
|
|
 |
|
  L. S. Chaturvedi, C. P. Gayer, H. M. Marsh, and M. D. Basson Repetitive deformation activates Src-independent FAK-dependent ERK motogenic signals in human Caco-2 intestinal epithelial cells Am J Physiol Cell Physiol, June 1, 2008; 294(6): C1350 - C1361. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. De Alvaro, I. Nieto-Vazquez, J. M. Rojas, and M. Lorenzo Nuclear Exclusion of Forkhead Box O and Elk1 and Activation of Nuclear Factor-{kappa}B Are Required for C2C12-RasV12C40 Myoblast Differentiation Endocrinology, February 1, 2008; 149(2): 793 - 801. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. K. Srivastava, X. Qin, N. Wedhas, M. Arnush, T. A. Linkhart, R. B. Chadwick, and A. Kumar Tumor Necrosis Factor-{alpha} Augments Matrix Metalloproteinase-9 Production in Skeletal Muscle Cells through the Activation of Transforming Growth Factor- -activated Kinase 1 (TAK1)-dependent Signaling Pathway J. Biol. Chem., November 30, 2007; 282(48): 35113 - 35124. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. M. Rice, D. H. Desai, D. L. Preston, P. S. Wehner, and E. R. Blough Vascular: Uniaxial stretch-induced regulation of mitogen-activated protein kinase, Akt and p70 S6 kinase in the ageing Fischer 344 x Brown Norway rat aorta Exp Physiol, September 1, 2007; 92(5): 963 - 970. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. L. Hammond, B. H. Simbi, and N. C. Stickland In ovo temperature manipulation influences embryonic motility and growth of limb tissues in the chick (Gallus gallus) J. Exp. Biol., August 1, 2007; 210(15): 2667 - 2675. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. J. Zhang, G. A. Truskey, and W. E. Kraus Effect of cyclic stretch on beta1D-integrin expression and activation of FAK and RhoA Am J Physiol Cell Physiol, June 1, 2007; 292(6): C2057 - C2069. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Dogra, S. L. Hall, N. Wedhas, T. A. Linkhart, and A. Kumar Fibroblast Growth Factor Inducible 14 (Fn14) Is Required for the Expression of Myogenic Regulatory Factors and Differentiation of Myoblasts into Myotubes: EVIDENCE FOR TWEAK-INDEPENDENT FUNCTIONS OF Fn14 DURING MYOGENESIS J. Biol. Chem., May 18, 2007; 282(20): 15000 - 15010. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. S. Chaturvedi, H. M. Marsh, and M. D. Basson Src and focal adhesion kinase mediate mechanical strain-induced proliferation and ERK1/2 phosphorylation in human H441 pulmonary epithelial cells Am J Physiol Cell Physiol, May 1, 2007; 292(5): C1701 - C1713. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. S. Chaturvedi, H. M. Marsh, X. Shang, Y. Zheng, and M. D. Basson Repetitive Deformation Activates Focal Adhesion Kinase and ERK Mitogenic Signals in Human Caco-2 Intestinal Epithelial Cells through Src and Rac1 J. Biol. Chem., January 5, 2007; 282(1): 14 - 28. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Dogra, H. Changotra, S. Mohan, and A. Kumar Tumor Necrosis Factor-like Weak Inducer of Apoptosis Inhibits Skeletal Myogenesis through Sustained Activation of Nuclear Factor-{kappa}B and Degradation of MyoD Protein J. Biol. Chem., April 14, 2006; 281(15): 10327 - 10336. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Wedhas, H. J. Klamut, C. Dogra, A. K. Srivastava, S. Mohan, and A. Kumar Inhibition of mechanosensitive cation channels inhibits myogenic differentiation by suppressing the expression of myogenic regulatory factors and caspase-3 activity FASEB J, December 1, 2005; 19(14): 1986 - 1997. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
