Document Detail


TNF-α/cycloheximide-induced oxidative stress and apoptosis in murine intestinal epithelial MODE-K cells.
MedLine Citation:
PMID:  22721505     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
In the mouse postoperative ileus model, we have shown an increase in oxidative stress after intestinal manipulation occurring earlier in the mucosa than in the muscular layer, which might contribute to epithelial barrier dysfunction. To address these findings in vitro, we assessed TNF-α/cycloheximide (CHX)-induced oxidative stress and apoptosis in a mouse intestinal epithelial cell line, MODE-K. The influence of heme oxygenase (HO)-1-related products and agents known to reduce reactive oxygen species (ROS) production on TNF-α/CHX-induced oxidative stress and apoptosis were investigated. MODE-K cells were exposed to different concentrations of TNF- α/CHX in the absence/presence of the test agents. Cell viability, caspase-3/7 activity, apoptosis, reduced glutathione level (GSH) and intracellular ROS production were measured. TNF-α/CHX decreased cell viability, increased caspase-3/7 activity, induced apoptosis, reduced the GSH level and increased ROS production in a concentration-dependent manner in MODE-K cells. All these effects of TNF- α/CHX were partially prevented by pretreatment with a carbon monoxide-releasing agent (CORM-A1) and nitrite. The antioxidant resveratrol abolished TNF-α/CHX-induced increase in ROS production and caspase-3/7 activity, but apoptosis was only partially prevented. MODE-K cells are sensitive to TNF-α-induced apoptosis in the presence of CHX, which is associated with increased intracellular ROS production and caspase-3/7 activation. The effects were partially mitigated by CORM-A1, nitrite and resveratrol. Thus, these agents could be of potential use in protecting the epithelial barrier against oxidative stress during intestinal ischemia/reperfusion injury.
Authors:
Dinesh Babu; Stefaan J Soenen; Koen Raemdonck; Georges Leclercq; Ole De Backer; Roberto Motterlini; Romain A Lefebvre
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Current pharmaceutical design     Volume:  18     ISSN:  1873-4286     ISO Abbreviation:  Curr. Pharm. Des.     Publication Date:  2012  
Date Detail:
Created Date:  2012-10-15     Completed Date:  2013-03-17     Revised Date:  2013-06-03    
Medline Journal Info:
Nlm Unique ID:  9602487     Medline TA:  Curr Pharm Des     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  4414-25     Citation Subset:  IM    
Affiliation:
Heymans Institute of Pharmacology, Faculty of Medicine and Health Sciences, Ghent University, Belgium.
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MeSH Terms
Descriptor/Qualifier:
Animals
Antioxidants / pharmacology
Apoptosis / drug effects*
Boranes / pharmacology
Carbonates / pharmacology
Caspase 3 / metabolism
Caspase 7 / metabolism
Cell Line
Cell Survival / drug effects
Cycloheximide / administration & dosage,  pharmacology*
Dose-Response Relationship, Drug
Epithelial Cells / drug effects,  metabolism
Heme Oxygenase-1 / metabolism
Intestinal Mucosa / cytology,  drug effects,  metabolism
Mice
Oxidative Stress / drug effects*
Reactive Oxygen Species / metabolism
Sodium Nitrite / pharmacology
Stilbenes / pharmacology
Tumor Necrosis Factor-alpha / administration & dosage,  metabolism,  pharmacology*
Chemical
Reg. No./Substance:
0/Antioxidants; 0/Boranes; 0/Carbonates; 0/Reactive Oxygen Species; 0/Stilbenes; 0/Tumor Necrosis Factor-alpha; 0/sodium boranocarbonate; 66-81-9/Cycloheximide; 7632-00-0/Sodium Nitrite; EC 1.14.99.3/Heme Oxygenase-1; EC 3.4.22.-/Caspase 3; EC 3.4.22.-/Caspase 7; Q369O8926L/resveratrol

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


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