| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
INFLAMMATION AND CYTOKINES
Departments of 1Surgery and 2Hematology/Oncology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts; and 3Department of Neurobiology, Ipsen Research Laboratories, Institut Henri Beaufour, Les Ulis, France
Submitted 14 September 2005 ; accepted in final form 25 January 2006
Muscle wasting in sepsis is a significant clinical problem because it results in muscle weakness and fatigue that may delay ambulation and increase the risk for thromboembolic and pulmonary complications. Treatments aimed at preventing or reducing muscle wasting in sepsis, therefore, may have important clinical implications. Recent studies suggest that sepsis-induced muscle proteolysis may be initiated by calpain-dependent release of myofilaments from the sarcomere, followed by ubiquitination and degradation of the myofilaments by the 26S proteasome. In the present experiments, treatment of rats with one of the calpain inhibitors calpeptin or BN82270 inhibited protein breakdown in muscles from rats made septic by cecal ligation and puncture. The inhibition of protein breakdown was not accompanied by reduced expression of the ubiquitin ligases atrogin-1/MAFbx and MuRF1, suggesting that the ubiquitin-proteasome system is regulated independent of the calpain system in septic muscle. When incubated muscles were treated in vitro with calpain inhibitor, protein breakdown rates and calpain activity were reduced, consistent with a direct effect in skeletal muscle. Additional experiments suggested that the effects of BN82270 on muscle protein breakdown may, in part, reflect inhibited cathepsin L activity, in addition to inhibited calpain activity. When cultured myoblasts were transfected with a plasmid expressing the endogenous calpain inhibitor calpastatin, the increased protein breakdown rates in dexamethasone-treated myoblasts were reduced, supporting a role of calpain activity in atrophying muscle. The present results suggest that treatment with calpain inhibitors may prevent sepsis-induced muscle wasting.
ubiquitin ligases; calpains
This article has been cited by other articles:
|
|
 |
|
  S. M. Phillips, E. I. Glover, and M. J. Rennie Alterations of protein turnover underlying disuse atrophy in human skeletal muscle J Appl Physiol, September 1, 2009; 107(3): 645 - 654. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Naderi, C. Bernreuther, N. Grabinski, C. T. Putman, B. Henkel, G. Bell, M. Glatzel, and K. R. Sultan Plasminogen Activator Inhibitor Type 1 Up-Regulation Is Associated with Skeletal Muscle Atrophy and Associated Fibrosis Am. J. Pathol., August 1, 2009; 175(2): 763 - 771. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. S. Supinski, J. Vanags, and L. A. Callahan Effect of proteasome inhibitors on endotoxin-induced diaphragm dysfunction Am J Physiol Lung Cell Mol Physiol, June 1, 2009; 296(6): L994 - L1001. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. S. Willis, J. C. Schisler, A. L. Portbury, and C. Patterson Build it up-Tear it down: protein quality control in the cardiac sarcomere Cardiovasc Res, February 15, 2009; 81(3): 439 - 448. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. M. McClung, A. R. Judge, E. E. Talbert, and S. K. Powers Calpain-1 is required for hydrogen peroxide-induced myotube atrophy Am J Physiol Cell Physiol, February 1, 2009; 296(2): C363 - C371. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. J. Smith, S. H. Lecker, and P.-O. Hasselgren Calpain activity and muscle wasting in sepsis Am J Physiol Endocrinol Metab, October 1, 2008; 295(4): E762 - E771. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. C. Vary, R. A. Frost, and C. H. Lang Acute alcohol intoxication increases atrogin-1 and MuRF1 mRNA without increasing proteolysis in skeletal muscle Am J Physiol Regulatory Integrative Comp Physiol, June 1, 2008; 294(6): R1777 - R1789. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. D. de Boer, A. Selby, P. Atherton, K. Smith, O. R. Seynnes, C. N. Maganaris, N. Maffulli, T. Movin, M. V. Narici, and M. J. Rennie The temporal responses of protein synthesis, gene expression and cell signalling in human quadriceps muscle and patellar tendon to disuse J. Physiol., November 15, 2007; 585(1): 241 - 251. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. M. W. Petersen, F. Magkos, P. Atherton, A. Selby, K. Smith, M. J. Rennie, B. K. Pedersen, and B. Mittendorfer Smoking impairs muscle protein synthesis and increases the expression of myostatin and MAFbx in muscle Am J Physiol Endocrinol Metab, September 1, 2007; 293(3): E843 - E848. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. S. Supinski and L. A. Callahan Free radical-mediated skeletal muscle dysfunction in inflammatory conditions J Appl Physiol, May 1, 2007; 102(5): 2056 - 2063. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Vermaelen, P. Sirvent, F. Raynaud, C. Astier, J. Mercier, A. Lacampagne, and O. Cazorla Differential localization of autolyzed calpains 1 and 2 in slow and fast skeletal muscles in the early phase of atrophy Am J Physiol Cell Physiol, May 1, 2007; 292(5): C1723 - C1731. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. J. Smith and S. L. Dodd Muscle: Calpain activation causes a proteasome-dependent increase in protein degradation and inhibits the Akt signalling pathway in rat diaphragm muscle Exp Physiol, May 1, 2007; 92(3): 561 - 573. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. A. Frost, G. J. Nystrom, L. S. Jefferson, and C. H. Lang Hormone, cytokine, and nutritional regulation of sepsis-induced increases in atrogin-1 and MuRF1 in skeletal muscle Am J Physiol Endocrinol Metab, February 1, 2007; 292(2): E501 - E512. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Dehoux, C. Gobier, P. Lause, L. Bertrand, J.-M. Ketelslegers, and J.-P. Thissen IGF-I does not prevent myotube atrophy caused by proinflammatory cytokines despite activation of Akt/Foxo and GSK-3beta pathways and inhibition of atrogin-1 mRNA Am J Physiol Endocrinol Metab, January 1, 2007; 292(1): E145 - E150. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. Wei, H. Yang, M. Menconi, P. Cao, C. E. Chamberlain, and P.-O. Hasselgren Treatment of cultured myotubes with the proteasome inhibitor beta-lactone increases the expression of the transcription factor C/EBPbeta Am J Physiol Cell Physiol, January 1, 2007; 292(1): C216 - C226. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Visit Other APS Journals Online |
