1. Lipopolysaccharide-induced intestinal motility disturbances are mediated by c-Jun NH2-terminal kinases.
- Author
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Gonzalo, Sergio, Grasa, Laura, Arruebo, María Pilar, Plaza, Miguel Ángel, and Murillo, María Divina
- Subjects
GASTROINTESTINAL motility ,ENDOTOXINS ,SEPSIS ,OXIDATIVE stress ,FREE radical pathophysiology ,MALONDIALDEHYDE ,GENE expression ,PROTEIN kinases ,SPECTROPHOTOMETRY - Abstract
Abstract: Background: Lipopolysaccharide (LPS) is a causative agent of sepsis. Many alterations, such as intestinal motility disturbances, have been attributed to LPS. Aims: Here we investigated the role of c-Jun NH
2 -terminal kinases (JNK) in the effect of LPS on intestinal motility, the oxidative stress status and the cyclooxygenese-2 (COX-2) expression. Methods: Rabbits were injected with either (1) saline, (2) LPS, (3) SP600125, a specific JNK inhibitor, or (4) SP600125+LPS. Duodenal contractility was studied in an organ bath. The formation of products of oxidative damage to proteins (carbonyls) and lipids [malondialdehyde (MDA) and 4-hydroxyalkenals (4-HDA)] was quantified by spectrophotometry in the intestine and plasma. The protein expression of p-JNK, total JNK, and COX-2 was measured by Western blot, and p-JNK was localized by immunohistochemistry. Results: LPS decreased the contractions evoked by acetylcholine and prostaglandin E2 and KCl-induced contractions. LPS increased phospho-JNK and COX-2 expressions and the levels of carbonyls and MDA+4-HDA. SP600125 blocked the effect of LPS on the acetylcholine, prostaglandin E2 , and KCl-induced contractions, the levels of carbonyls and MDA+4-HDA, and the p-JNK and COX-2 expressions. p-JNK was detected in the smooth muscle cells of duodenum. Conclusion: Our results suggest that JNK is involved in the mechanism of action of LPS in the intestine. [Copyright &y& Elsevier]- Published
- 2011
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