| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Department of Medicine, Baylor College of Medicine, Houston, Texas, USA
1Correspondence: Baylor College of Medicine, One Baylor Plaza, Department of Medicine, Pulmonary Section, Suite 520B, Houston, TX 77030, USA. E-mail: boriek{at}bcm.tmc.edu
Dystrophin is a cytoskeletal protein found at the inner surface of skeletal and cardiac muscle fibers. We hypothesize that deficiency of dystrophin increases muscle compliance and causes an aberrant mechanotransduction in muscle fibers. To test this hypothesis, we measured the length–tension relationships and determined intracellular signaling leading to the activation of mitogen-activated protein (MAP) kinases in diaphragm muscle fibers from dystrophin-deficient mdx mice. Compared with controls, length–tension curves of the mdx mice were shifted to the right. A higher level of activation of extracellular signal-regulated kinase 1/2 (ERK1/2) but not c-Jun N-terminal kinase-1 or p38 MAP kinase was observed in the mdx muscle compared with the normal muscle in response to mechanical stretch. Removal of Ca2+ from the medium inhibited stretch-induced ERK1/2 activation only in mdx muscle fibers but not in the normal fibers. Conversely, pretreatment with TMB-8 (an antagonist of intracellular Ca2+) blocked the mechanical stretch-induced ERK1/2 activation in normal but not in mdx muscle fibers. Pretreatment of muscle with nifedipine (L-type calcium channel antagonist) marginally decreased the activation of ERK1/2 in normal or mdx muscle whereas pretreatment with gadolinium (III) chloride (an inhibitor of stretch-activated channels) only blocked the activation of ERK1/2 in mdx muscle, with no significant effect on normal muscle. A higher basal level of activation of activator protein-1 (AP-1) transcription factor was observed in dystrophin-deficient diaphragm, which was further augmented by mechanical stretch. Mechanical stretch-induced activation of AP-1 was decreased by pretreatment of muscle fibers with PD98059 (ERK1/2 inhibitor) and removal of Ca2+ ions from incubation medium. Our results show that dystrophin is a load-bearing element and its deficiency leads to loss of muscle stiffness and aberrant mechanotransduction in skeletal muscle fibers.—Kumar, A., Khandelwal, N., Malya, R., Reid, M. B., Boriek, A. M. Loss of dystrophin causes aberrant mechanotransduction in skeletal muscle fibers.
Key Words: dystrophin • skeletal muscle • MAP kinases • AP-1 • mechanotransduction
This article has been cited by other articles:
|
|
 |
|
  R. Ng, J. M. Metzger, D. R. Claflin, and J. A. Faulkner Poloxamer 188 reduces the contraction-induced force decline in lumbrical muscles from mdx mice Am J Physiol Cell Physiol, July 1, 2008; 295(1): C146 - C150. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 O. Friedrich, C. Weber, F. v. Wegner, J. S. Chamberlain, and R. H. A. Fink Unloaded Speed of Shortening in Voltage-Clamped Intact Skeletal Muscle Fibers from wt, mdx, and Transgenic Minidystrophin Mice Using a Novel High-Speed Acquisition System Biophys. J., June 15, 2008; 94(12): 4751 - 4765. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Hnia, J. Gayraud, G. Hugon, M. Ramonatxo, S. De La Porte, S. Matecki, and D. Mornet L-Arginine Decreases Inflammation and Modulates the Nuclear Factor-{kappa}B/Matrix Metalloproteinase Cascade in Mdx Muscle Fibers Am. J. Pathol., June 1, 2008; 172(6): 1509 - 1519. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. J. Kosek and M. M. Bamman Modulation of the dystrophin-associated protein complex in response to resistance training in young and older men J Appl Physiol, May 1, 2008; 104(5): 1476 - 1484. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Iwata, Y. Katanosaka, T. Hisamitsu, and S. Wakabayashi Enhanced Na+/H+ Exchange Activity Contributes to the Pathogenesis of Muscular Dystrophy via Involvement of P2 Receptors Am. J. Pathol., November 1, 2007; 171(5): 1576 - 1587. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Gailly, F. De Backer, M. Van Schoor, and J. M. Gillis In situ measurements of calpain activity in isolated muscle fibres from normal and dystrophin-lacking mdx mice J. Physiol., August 1, 2007; 582(3): 1261 - 1275. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Hnia, G. Hugon, F. Rivier, A. Masmoudi, J. Mercier, and D. Mornet Modulation of p38 Mitogen-Activated Protein Kinase Cascade and Metalloproteinase Activity in Diaphragm Muscle in Response to Free Radical Scavenger Administration in Dystrophin-Deficient Mdx Mice Am. J. Pathol., February 1, 2007; 170(2): 633 - 643. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. E. Ingber Cellular mechanotransduction: putting all the pieces together again FASEB J, May 1, 2006; 20(7): 811 - 827. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. M. Judge, M. Haraguchiln, and J. S. Chamberlain Dissecting the signaling and mechanical functions of the dystrophin-glycoprotein complex J. Cell Sci., April 15, 2006; 119(8): 1537 - 1546. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. M. Hanft, I. N. Rybakova, J. R. Patel, J. A. Rafael-Fortney, and J. M. Ervasti Cytoplasmic {gamma}-actin contributes to a compensatory remodeling response in dystrophin-deficient muscle PNAS, April 4, 2006; 103(14): 5385 - 5390. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. W.R. Dudley, G. Danialou, K. Govindaraju, L. Lands, D. E. Eidelman, and B. J. Petrof Sarcolemmal Damage in Dystrophin Deficiency Is Modulated by Synergistic Interactions between Mechanical and Oxidative/Nitrosative Stresses Am. J. Pathol., April 1, 2006; 168(4): 1276 - 1287. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. R. Barton Impact of sarcoglycan complex on mechanical signal transduction in murine skeletal muscle Am J Physiol Cell Physiol, February 1, 2006; 290(2): C411 - C419. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Zolkiewska Ecto-ADP-ribose Transferases: Cell-Surface Response to Local Tissue Injury Physiology, December 1, 2005; 20(6): 374 - 381. [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]
|
|
|
|
|
|
J. V. Chakkalakal, J. Thompson, R. J. Parks, and B. J. Jasmin Molecular, cellular, and pharmacological therapies for Duchenne/Becker muscular dystrophies FASEB J, June 1, 2005; 19(8): 880 - 891. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. A. Griffin, H. Feng, M. Tewari, P. Acosta, M. Kawana, H. L. Sweeney, and D. E. Discher {gamma}-Sarcoglycan deficiency increases cell contractility, apoptosis and MAPK pathway activation but does not affect adhesion J. Cell Sci., April 1, 2005; 118(7): 1405 - 1416. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. De Luca, B. Nico, A. Liantonio, M. P. Didonna, B. Fraysse, S. Pierno, R. Burdi, D. Mangieri, J.-F. Rolland, C. Camerino, et al. A Multidisciplinary Evaluation of the Effectiveness of Cyclosporine A in Dystrophic Mdx Mice Am. J. Pathol., February 1, 2005; 166(2): 477 - 489. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. KUMAR, R. MURPHY, P. ROBINSON, L. WEI, and A. M. BORIEK Cyclic mechanical strain inhibits skeletal myogenesis through activation of focal adhesion kinase, Rac-1 GTPase, and NF-{kappa}B transcription factor FASEB J, October 1, 2004; 18(13): 1524 - 1535. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Matecki, G. H. Guibinga, and B. J. Petrof Regenerative capacity of the dystrophic (mdx) diaphragm after induced injury Am J Physiol Regulatory Integrative Comp Physiol, October 1, 2004; 287(4): R961 - R968. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
