Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.11.24 (mitogen-activated protein kinase)
 95,810 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hemorrhagic shock and resuscitation cause endotoxemia and hepatocellular damage. Because lipopolysaccharide-binding protein (LBP) enhances cellular responses to endotoxin, our aim was to determine whether LBP contributes to hemorrhage/resuscitation-induced injury by comparing LBP knockout and wild-type mice. Under pentobarbital anaesthesia, wild-type and LBP-deficient mice were hemorrhaged to 30 mmHg for 3 h and then resuscitated with shed blood plus half the volume of lactated Ringer solution. Serum alanine aminotransferase (ALT) necrosis, neutrophil infiltration, and 4-hydroxynonenal by histology/cytochemistry and stress kinase activation by immunoblot analysis were then determined. ALT in wild-type mice was 2,461 +/- 383 and 1,418 +/- 194 IU/l (means +/- SE), respectively, at 2 and 6 h after resuscitation versus sham ALT of 102 +/- 6 IU/l. In LBP-deficient mice, ALT was blunted at both time points to 1,108 +/- 340 and 619 +/- 171 IU/l (P < 0.05). Liver necrosis after 6 h was also attenuated from 3.5 +/- 0.8% in wild-type mice to 1.3 +/- 0.5% in LBP-deficient mice (P < 0.05). After hemorrhage/resuscitation, neutrophil infiltration increased 71% more in wild-type than LBP knockout mice. Similarly, hepatic 4-hydroxynonenal staining, indicative of lipid peroxidation, decreased from 33.8 +/- 4.5% in wild-type mice to 11.6 +/- 1.9% in knockout mice (P < 0.05). After hemorrhage/resuscitation, activation of MAPKs, JNK and ERK, occurred in wild-type mice, which was largely blocked in LBP-deficient mice. However, endotoxin in portal blood after resuscitation was not significantly different between wild-type and knockout mice. In conclusion, hemorrhagic shock and resuscitation to mice cause severe, LBP-mediated hepatocellular damage. An absence of LBP blunts hepatocellular injury with decreased neutrophil infiltration, oxidative stress, and c-Jun and ERK activation.
 ...
PMID:Lipopolysaccharide-binding protein modulates hepatic damage and the inflammatory response after hemorrhagic shock and resuscitation. 1661 72

Oxidative stress is known to produce tissue injury and to activate various signaling pathways. To investigate the molecular events linked to acute oxidative stress in mouse liver, we injected a toxic dose of paraquat. Liver necrosis was first observed, followed by histological marks of cell proliferation. Concomitantly, activation of the MAP kinase pathway and increased levels of the anti-apoptotic protein Bcl-XL were observed. Gene expression profiles revealed that the differentially expressed genes were potentially involved in cell proliferation. These data suggest that paraquat-induced acute oxidative stress triggers the activation of regeneration-related events in the liver.
 ...
PMID:Acute oxidative stress is associated with cell proliferation in the mouse liver. 1679 15