Document Detail

CaM kinase II in colonic smooth muscle contributes to dysmotility in murine DSS-colitis.
MedLine Citation:
PMID:  19735476     Owner:  NLM     Status:  MEDLINE    
BACKGROUND: Altered calcium mobilization has been implicated in the development of colonic dysmotility in inflammatory bowel disease. The aim of this study was to investigate the mechanisms by which disrupted intracellular Ca(2+) signalling contributes to the impaired contractility of colon circular smooth muscles.
METHODS: Acute colitis was induced in C57Bl/6 mice with dextran sulphate sodium (DSS) in the drinking water for 5 days.
KEY RESULTS: Spontaneous and acetylcholine-evoked contractions, caffeine-evoked hyperpolarization, and SERCA2 and phospholamban expression were reduced compared with controls. Tetrodotoxin did not restore control levels of contractile activity. The amplitudes, but not the frequency, of intracellular Ca(2+) waves were increased compared with controls. Caffeine abolished intracellular Ca(2+) waves in control smooth muscle cells, but not in smooth muscle cells from DSS-treated mice. CaM kinase II activity and cytosolic levels of HDAC4 were increased, and I kappaB alpha levels were decreased in distal colon smooth muscles from DSS-treated mice.
CONCLUSIONS & INFERENCES: These results suggest that disruptions in intracellular Ca(2+) mobilization due to down-regulation of SERCA2 and phospholamban expression lead to increased CaM kinase II activity and cytosolic HDAC4 that may contribute to the dysmotility of colonic smooth muscles in colitis by enhancing NF-kappaB activity.
S Qureshi; J Song; H-T Lee; S D Koh; G W Hennig; B A Perrino
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2009-09-07
Journal Detail:
Title:  Neurogastroenterology and motility : the official journal of the European Gastrointestinal Motility Society     Volume:  22     ISSN:  1365-2982     ISO Abbreviation:  Neurogastroenterol. Motil.     Publication Date:  2010 Feb 
Date Detail:
Created Date:  2010-01-13     Completed Date:  2010-03-31     Revised Date:  2013-05-31    
Medline Journal Info:
Nlm Unique ID:  9432572     Medline TA:  Neurogastroenterol Motil     Country:  England    
Other Details:
Languages:  eng     Pagination:  186-95, e64     Citation Subset:  IM    
Department of Physiology and Cell Biology, Center of Biomedical Research Excellence, University of Nevada School of Medicine, Reno, NV 89557, USA.
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MeSH Terms
Acetylcholine / pharmacology
Action Potentials / drug effects,  physiology
Blotting, Western
Caffeine / pharmacology
Calcium Signaling / drug effects,  physiology
Calcium-Binding Proteins / metabolism
Calcium-Calmodulin-Dependent Protein Kinase Type 2 / metabolism*
Colitis / chemically induced,  metabolism,  physiopathology*
Colon / drug effects,  metabolism*,  physiopathology
Dextran Sulfate / toxicity
Gastrointestinal Motility / drug effects,  physiology*
Muscle Contraction / drug effects,  physiology*
Muscle, Smooth / drug effects,  metabolism*,  physiopathology
Sarcoplasmic Reticulum Calcium-Transporting ATPases / metabolism
Time Factors
Grant Support
Reg. No./Substance:
0/Calcium-Binding Proteins; 0/phospholamban; 51-84-3/Acetylcholine; 58-08-2/Caffeine; 9042-14-2/Dextran Sulfate; EC Protein Kinase Type 2; EC protein, mouse; EC Reticulum Calcium-Transporting ATPases

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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