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Calpain‐1 inhibitor prevent loss of dystrophin in experimental septic cardiomyopathy induced by cecal ligation and puncture (CLP)
Author(s) -
Freitas Ana C.S.,
Figueiredo Maria J,
Ferezin Patricia,
Campos Erica C.,
Rossi Marcos A.,
Celes Mara R
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.lb479
Subject(s) - calpain , sepsis , dystrophin , leupeptin , medicine , western blot , pharmacology , immunology , andrology , chemistry , muscular dystrophy , enzyme , protease , biochemistry , gene
This study was designed to test the hypothesis that N‐Acetyl‐Lleucyl‐L‐leucyl‐L‐norleucinal (ALLN), calpain‐1 inhibitor, could attenuate dystrophin disruption and cardiac contractile proteins loss/reduction in experimental sepsis induced by CLP. Male C57Bl/6 mice were subjected to sham and severe septic injury (SSI) induced by CLP. Half of animals from each group were treated with ALLN (3mg/kg, SSI+ALLN; SH+ALLN) 4hs after surgery. In SSI+ALLN mice reduced amounts of myocardial calpain‐1 were associated with increased actin/myosin expression as compared to SSI mice. Additionally, ALLN treatment of septic mice significantly prevented loss of dystrophin and â‐dystroglycan as compared to SSI mice. Concurrently, SSI+ALLN mice presented an increased survival rate. Calpain inhibitor, ALLN, suppressed the increased calpain‐1 expression and prevented myocardial structural injury caused by experimental severe sepsis. These observations reinforce the concept that calpain‐1 activation represents a key target in dystrophin disruption behind cardiac dysfunction in severe sepsis/septic shock. Further studies are needed to elucidate this mechanism that may provide new interventional pathways to prevent septic cardiomyopathy.