Journal
PLOS ONE
Volume 11, Issue 11, Pages -Publisher
PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pone.0166839
Keywords
-
Categories
Funding
- FAPESP (Fundacao Amparo a Pesquisa do Estado de Sao Paulo) [07/58843-2, 12/23649-0, 12/17542-8]
- CNPq (Conselho Nacional de Desenvolvimento Cientifico e Tecnologico) [303308/2013-3]
- Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP) [12/23649-0, 12/17542-8] Funding Source: FAPESP
Ask authors/readers for more resources
Cardiac dysfunction caused by the impairment of myocardial contractility has been recognized as an important factor contributing to the high mortality in sepsis. Calpain activation in the heart takes place in response to increased intracellular calcium influx resulting in proteolysis of structural and contractile proteins with subsequent myocardial dysfunction. The purpose of the present study was to test the hypothesis that increased levels of calpain in the septic heart leads to disruption of structural and contractile proteins and that administration of calpain inhibitor-1 (N-acetyl-leucinyl-leucinyl-norleucinal (ALLN)) after sepsis induced by cecal ligation and puncture prevents cardiac protein degradation. We also tested the hypothesis that calpain plays a role in the modulation of protein synthesis/degradation through the activation of proteasome-dependent proteolysis and inhibition of the mTOR pathway. Severe sepsis significantly increased heart calpain-1 levels and promoted ubiquitin and Pa28 beta over-expression with a reduction in the mTOR levels. In addition, sepsis reduced the expression of structural proteins dystrophin and beta-dystroglycan as well as the contractile proteins actin and myosin. ALLN administration prevented sepsis-induced increases in calpain and ubiquitin levels in the heart, which resulted in decreased of structural and contractile proteins degradation and basal mTOR expression levels were re-established. Our results support the concept that increased calpain concentrations may be part of an important mechanism of sepsis-induced cardiac muscle proteolysis.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available