BIOMAT Database Logo BIOMAT Database Logo

Nuclear factor-kappaB activation by edema inhibits intestinal contractile activity. 2010

Karen S Uray, and Zachary Wright, and Karina Kislitsyna, and Hasen Xue, and Charles S Cox
Department of Pediatric Surgery, University of Texas Medical School at Houston, Houston, TX, USA.

OBJECTIVE To investigate the molecular mechanisms leading to edema-induced decreases in intestinal smooth muscle myosin light-chain phosphorylation. Intestinal interstitial edema often develops during abdominal surgery and after fluid resuscitation in trauma patients. Intestinal edema causes decreased intestinal contractile activity via decreased intestinal smooth muscle myosin light-chain phosphorylation, leading to slower intestinal transit. Interstitial edema development is a complex phenomenon, resulting in many changes to the interstitial environment surrounding intestinal smooth muscle cells. Thus, the mechanism(s) by which intestinal edema development causes intestinal dysfunction are likely to be multifactorial. METHODS Randomized animal study. METHODS University laboratory. METHODS Male Sprague-Dawley rats, weighing 250-350 g. METHODS Studies were performed in a rat model in which a combination of mesenteric venous hypertension and administration of resuscitative fluids induces intestinal edema, mimicking the clinical setting of damage control resuscitation. RESULTS Microarray analysis of edematous intestinal smooth muscle combined with an in silico search for overrepresented transcription factor binding sites revealed the involvement of nuclear factor-kappaB in edema-induced intestinal dysfunction. Nuclear factor-kappaB deoxyribonucleic acid binding activity was significantly increased in edematous intestinal smooth muscle compared with controls. Inhibition of nuclear factor-kappaB activation blocked edema-induced decreases in basal intestinal contractile activity. Inhibition of nuclear factor-kappaB activation also attenuated edema-induced decreases in myosin light-chain phosphorylation. CONCLUSIONS We conclude that intestinal edema activates nuclear factor-kappaB, which, in turn, triggers a gene regulation program that eventually leads to decreased myosin light-chain phosphorylation and, thus, decreased intestinal contractile activity.

UI MeSH Term Description Entries
D007410 Intestinal Diseases Pathological processes in any segment of the INTESTINE from DUODENUM to RECTUM. Disease, Intestinal,Diseases, Intestinal,Intestinal Disease
D008297 Male Males
D009130 Muscle, Smooth Unstriated and unstriped muscle, one of the muscles of the internal organs, blood vessels, hair follicles, etc. Contractile elements are elongated, usually spindle-shaped cells with centrally located nuclei. Smooth muscle fibers are bound together into sheets or bundles by reticular fibers and frequently elastic nets are also abundant. (From Stedman, 25th ed) Muscle, Involuntary,Smooth Muscle,Involuntary Muscle,Involuntary Muscles,Muscles, Involuntary,Muscles, Smooth,Smooth Muscles
D010766 Phosphorylation The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety. Phosphorylations
D012151 Resuscitation The restoration to life or consciousness of one apparently dead. (Dorland, 27th ed) Resuscitations
D004487 Edema Abnormal fluid accumulation in TISSUES or body cavities. Most cases of edema are present under the SKIN in SUBCUTANEOUS TISSUE. Dropsy,Hydrops,Anasarca
D005440 Fluid Therapy Therapy whose basic objective is to restore the volume and composition of the body fluids to normal with respect to WATER-ELECTROLYTE BALANCE. Fluids may be administered intravenously, orally, by intermittent gavage, or by HYPODERMOCLYSIS. Oral Rehydration Therapy,Rehydration,Rehydration, Oral,Oral Rehydration,Rehydration Therapy, Oral,Therapy, Fluid,Therapy, Oral Rehydration,Fluid Therapies,Oral Rehydration Therapies,Oral Rehydrations,Rehydration Therapies, Oral,Rehydrations,Rehydrations, Oral,Therapies, Fluid,Therapies, Oral Rehydration
D005769 Gastrointestinal Motility The motor activity of the GASTROINTESTINAL TRACT. Intestinal Motility,Gastrointestinal Motilities,Intestinal Motilities,Motilities, Gastrointestinal,Motilities, Intestinal,Motility, Gastrointestinal,Motility, Intestinal
D005786 Gene Expression Regulation Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation. Gene Action Regulation,Regulation of Gene Expression,Expression Regulation, Gene,Regulation, Gene Action,Regulation, Gene Expression
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia

Related Publications

Karen S Uray, and Zachary Wright, and Karina Kislitsyna, and Hasen Xue, and Charles S Cox
Thiopental inhibits the activation of nuclear factor kappaB.
May 2002, Anesthesiology,
Karen S Uray, and Zachary Wright, and Karina Kislitsyna, and Hasen Xue, and Charles S Cox
Thiopental inhibits tumor necrosis factor alpha-induced activation of nuclear factor kappaB through suppression of kappaB kinase activity.
August 2003, Anesthesiology,
Karen S Uray, and Zachary Wright, and Karina Kislitsyna, and Hasen Xue, and Charles S Cox
Guggulsterone inhibits osteoclastogenesis induced by receptor activator of nuclear factor-kappaB ligand and by tumor cells by suppressing nuclear factor-kappaB activation.
January 2006, Clinical cancer research : an official journal of the American Association for Cancer Research,
Karen S Uray, and Zachary Wright, and Karina Kislitsyna, and Hasen Xue, and Charles S Cox
Arsenite inhibits interleukin-6 production in human intestinal epithelial cells by down-regulating nuclear factor-kappaB activity.
October 2002, Clinical science (London, England : 1979),
Karen S Uray, and Zachary Wright, and Karina Kislitsyna, and Hasen Xue, and Charles S Cox
Sulforaphane inhibits osteoclastogenesis by inhibiting nuclear factor-kappaB.
December 2005, Molecules and cells,
Karen S Uray, and Zachary Wright, and Karina Kislitsyna, and Hasen Xue, and Charles S Cox
Kallistatin inhibits vascular inflammation by antagonizing tumor necrosis factor-alpha-induced nuclear factor kappaB activation.
August 2010, Hypertension (Dallas, Tex. : 1979),
Karen S Uray, and Zachary Wright, and Karina Kislitsyna, and Hasen Xue, and Charles S Cox
Vasoactive intestinal peptide inhibits IL-8 production in human monocytes by downregulating nuclear factor kappaB-dependent transcriptional activity.
March 2003, Biochemical and biophysical research communications,
Karen S Uray, and Zachary Wright, and Karina Kislitsyna, and Hasen Xue, and Charles S Cox
Fas-associated factor-1 inhibits nuclear factor-kappaB (NF-kappaB) activity by interfering with nuclear translocation of the RelA (p65) subunit of NF-kappaB.
January 2004, The Journal of biological chemistry,
Karen S Uray, and Zachary Wright, and Karina Kislitsyna, and Hasen Xue, and Charles S Cox
Activation of nuclear factor-kappaB.
January 2006, Methods in molecular biology (Clifton, N.J.),
Karen S Uray, and Zachary Wright, and Karina Kislitsyna, and Hasen Xue, and Charles S Cox
Decursin inhibits induction of inflammatory mediators by blocking nuclear factor-kappaB activation in macrophages.
June 2006, Molecular pharmacology,
Copied contents to your clipboard!