calpain and Shock--Septic

calpain has been researched along with Shock--Septic* in 3 studies

Other Studies

3 other study(ies) available for calpain and Shock--Septic

ArticleYear
The p110δ isoform of the kinase PI(3)K controls the subcellular compartmentalization of TLR4 signaling and protects from endotoxic shock.
    Nature immunology, 2012, Volume: 13, Issue:11

    Lipopolysaccharide activates plasma-membrane signaling and endosomal signaling by Toll-like receptor 4 (TLR4) through the TIRAP-MyD88 and TRAM-TRIF adaptor complexes, respectively, but it is unclear how the signaling switch between these cell compartments is coordinated. In dendritic cells, we found that the p110δ isoform of phosphatidylinositol-3-OH kinase (PI(3)K) induced internalization of TLR4 and dissociation of TIRAP from the plasma membrane, followed by calpain-mediated degradation of TIRAP. Accordingly, inactivation of p110δ prolonged TIRAP-mediated signaling from the plasma membrane, which augmented proinflammatory cytokine production while decreasing TRAM-dependent endosomal signaling that generated anti-inflammatory cytokines (interleukin 10 and interferon-β). In line with that altered signaling output, p110δ-deficient mice showed enhanced endotoxin-induced death. Thus, by controlling the 'topology' of TLR4 signaling complexes, p110δ balances overall homeostasis in the TLR4 pathway.

    Topics: Animals; Calpain; Cell Compartmentation; Cell Membrane; Cells, Cultured; Class Ia Phosphatidylinositol 3-Kinase; Dendritic Cells; Endosomes; Gene Expression; Interferon-beta; Interleukin-10; Isoenzymes; Lipopolysaccharides; Membrane Glycoproteins; Mice; Mice, Knockout; Receptors, Interleukin; Receptors, Interleukin-1; Shock, Septic; Signal Transduction; Toll-Like Receptor 4

2012
Nuclear factor-kappaB inhibition in sepsis: steroids versus specific nuclear factor-kappaB inhibitors?
    Critical care medicine, 2002, Volume: 30, Issue:10

    Topics: Animals; Calpain; Glucocorticoids; Glycoproteins; Multiple Organ Failure; NF-kappa B; Rats; Shock, Septic

2002
Effect of calpain inhibitor I, an inhibitor of the proteolysis of I kappa B, on the circulatory failure and multiple organ dysfunction caused by endotoxin in the rat.
    British journal of pharmacology, 1997, Volume: 121, Issue:4

    1. We compared the effects of calpain inhibitor I (inhibitor of the proteolysis of I kappa B and, hence, of the activation of nuclear factor kappa B (NF kappa B) and dexamethasone on (i) the circulatory failure, (ii) multiple organ dysfunction and (iii) induction of the inducible isoforms of nitric oxide (NO) synthase (iNOS) and cyclo-oxygenase (COX-2) in anaesthetized rats with endotoxic shock. 2. Injection of lipopolysaccharide (LPS, E. coli, 10 mg kg-1, i.v.) resulted in hypotension and a reduction of the pressor responses elicited by noradrenaline. This circulatory dysfunction was attenuated by pretreatment of LPS-rats with calpain inhibitor I (10 mg kg-1, i.v., 2 h before LPS) or dexamethasone (1 mg kg-1, i.v.). 3. Endotoxaemia also caused rises in the serum levels of (i) urea and creatinine (renal dysfunction), (ii) alanine aminotransferase (ALT), aspartate aminotransferase (AST) (hepatocellular injury), bilirubin and gamma-glutamyl transferase (gamma GT) (liver dysfunction), (iii) lipase (pancreatic injury) and (iv) lactate. Calpain inhibitor I and dexamethasone attenuated the liver injury, the pancreatic injury, the lactic acidosis as well as the hypoglycaemia caused by LPS. Dexamethasone, but not calpain inhibitor I, reduced the renal dysfunction caused by LPS. 4. Endotoxaemia for 6 h resulted in a substantial increase in iNOS and COX-2 protein and activity in lung and liver, which was attenuated in LPS-rats pretreated with calpain inhibitor I or dexamethasone. 5. Thus, calpain inhibitor I and dexamethasone attenuate (i) the circulatory failure, (ii) the multiple organ dysfunction (liver and pancreatic dysfunction/injury, lactic acidosis, hypoglycaemia), as well as (iii) the induction of iNOS and COX-2 protein and activity in rats with endotoxic shock. We propose that prevention of the activation of NF-kappa B in vivo may be useful in the therapy of circulatory shock or of disorders associated with local or systemic inflammation.

    Topics: 6-Ketoprostaglandin F1 alpha; Animals; Calpain; Cysteine Proteinase Inhibitors; Dexamethasone; DNA-Binding Proteins; Endotoxemia; I-kappa B Proteins; Lipopolysaccharides; Male; Mice; Multiple Organ Failure; Nitric Oxide Synthase; Proto-Oncogene Proteins; Rats; Rats, Wistar; Shock, Septic; Tosylphenylalanyl Chloromethyl Ketone; Tumor Necrosis Factor-alpha

1997