| 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
Submitted 26 May 2004 ; accepted in final form 15 November 2004
We examined the influence of sepsis on the expression and activity of the calpain and caspase systems in skeletal muscle. Sepsis was induced in rats by cecal ligation and puncture (CLP). Control rats were sham operated. Calpain activity was determined by measuring the calcium-dependent hydrolysis of casein and by casein zymography. The activity of the endogenous calpain inhibitor calpastatin was measured by determining the inhibitory effect on calpain activity in muscle extracts. Protein levels of µ- and m-calpain and calpastatin were determined by Western blotting, and calpastatin mRNA was measured by real-time PCR. Caspase-3 activity was determined by measuring the hydrolysis of the fluorogenic caspase-3 substrate Ac-DEVD-AMC and by determining protein and mRNA expression for caspase-3 by Western blotting and real-time PCR, respectively. In addition, the role of calpains and caspase-3 in sepsis-induced muscle protein breakdown was determined by measuring protein breakdown rates in the presence of specific inhibitors. Sepsis resulted in increased muscle calpain activity caused by reduced calpastatin activity. In contrast, caspase-3 activity, mRNA levels, and activated caspase-3 29-kDa fragment were not altered in muscle from septic rats. Sepsis-induced muscle proteolysis was blocked by the calpain inhibitor calpeptin but was not influenced by the caspase-3 inhibitor Ac-DEVD-CHO. The results suggest that sepsis-induced muscle wasting is associated with increased calpain activity, secondary to reduced calpastatin activity, and that caspase-3 activity is not involved in the catabolic response to sepsis.
muscle wasting; sepsis; calpains; calpastatin; caspase-3; proteolysis
This article has been cited by other articles:
|
|
 |
|
  M. V. Rao, P. S. Mohan, C. M. Peterhoff, D.-S. Yang, S. D. Schmidt, P. H. Stavrides, J. Campbell, Y. Chen, Y. Jiang, P. A. Paskevich, et al. Marked Calpastatin (CAST) Depletion in Alzheimer's Disease Accelerates Cytoskeleton Disruption and Neurodegeneration: Neuroprotection by CAST Overexpression J. Neurosci., November 19, 2008; 28(47): 12241 - 12254. [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]
|
|
|
|
 |
|
 B. T. Workeneh, H. Rondon-Berrios, L. Zhang, Z. Hu, G. Ayehu, A. Ferrando, J. D. Kopple, H. Wang, T. Storer, M. Fournier, et al. Development of a Diagnostic Method for Detecting Increased Muscle Protein Degradation in Patients with Catabolic Conditions J. Am. Soc. Nephrol., November 1, 2006; 17(11): 3233 - 3239. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. H. Lecker, A. L. Goldberg, and W. E. Mitch Protein Degradation by the Ubiquitin-Proteasome Pathway in Normal and Disease States J. Am. Soc. Nephrol., July 1, 2006; 17(7): 1807 - 1819. [Full Text] [PDF]
|
|
|
|
 |
|
 M. U. Fareed, A. R. Evenson, W. Wei, M. Menconi, V. Poylin, V. Petkova, B. Pignol, and P.-O. Hasselgren Treatment of rats with calpain inhibitors prevents sepsis-induced muscle proteolysis independent of atrogin-1/MAFbx and MuRF1 expression Am J Physiol Regulatory Integrative Comp Physiol, June 1, 2006; 290(6): R1589 - R1597. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. Kramerova, E. Kudryashova, G. Venkatraman, and M. J. Spencer Calpain 3 participates in sarcomere remodeling by acting upstream of the ubiquitin-proteasome pathway Hum. Mol. Genet., August 1, 2005; 14(15): 2125 - 2134. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Visit Other APS Journals Online |
