| Protective effects of nonionic triblock copolymers on bile acid-mediated epithelial barrier disruption. | |
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MedLine Citation:
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PMID: 21937955 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Translocation of bacteria and other luminal factors from the intestine following surgical injury can be a major driver of critical illness. Bile acids have been shown to play a key role in the loss of intestinal epithelial barrier function during states of host stress. Experiments to study the ability of nonionic block copolymers to abrogate barrier failure in response to bile acid exposure are described. In vitro experiments were performed with the bile salt sodium deoxycholate on Caco-2 enterocyte monolayers using transepithelial electrical resistance to assay barrier function. A bisphenol A coupled triblock polyethylene glycol (PEG), PEG 15-20, was shown to prevent sodium deoxycholate-induced barrier failure. Enzyme-linked immunosorbent assay, lactate dehydrogenase, and caspase 3-based cell death detection assays demonstrated that bile acid-induced apoptosis and necrosis were prevented with PEG 15-20. Immunofluorescence microscopic visualization of the tight junctional protein zonula occludens 1 (ZO-1) demonstrated that PEG 15-20 prevented significant changes in tight junction organization induced by bile acid exposure. Preliminary transepithelial electrical resistance-based studies examining structure-function correlates of polymer protection against bile acid damage were performed with a small library of PEG-based copolymers. Polymer properties associated with optimal protection against bile acid-induced barrier disruption were PEG-based compounds with a molecular weight greater than 10 kd and amphiphilicity. The data demonstrate that PEG-based copolymer architecture is an important determinant that confers protection against bile acid injury of intestinal epithelia. |
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Authors:
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Adam Edelstein; David Fink; Mark Musch; Vesta Valuckaite; Olga Zaborina; Simonida Grubjesic; Millicent A Firestone; Jeffrey B Matthews; John C Alverdy |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural |
Journal Detail:
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Title: Shock (Augusta, Ga.) Volume: 36 ISSN: 1540-0514 ISO Abbreviation: Shock Publication Date: 2011 Nov |
Date Detail:
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Created Date: 2011-10-18 Completed Date: 2012-05-16 Revised Date: 2013-02-19 |
Medline Journal Info:
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Nlm Unique ID: 9421564 Medline TA: Shock Country: United States |
Other Details:
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Languages: eng Pagination: 451-7 Citation Subset: IM |
Affiliation:
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Department of Surgery, Pritzker School of Medicine, University of Chicago, 5841 S Maryland Ave., Chicago, IL 60637, USA.. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Apoptosis
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drug effects Bile Acids and Salts / pharmacology* Caco-2 Cells Caspase 3 / metabolism Deoxycholic Acid / pharmacology Humans Intestinal Mucosa / drug effects* Membrane Proteins / metabolism Microscopy, Fluorescence Necrosis / chemically induced, prevention & control Phenols / chemistry Phosphoproteins / metabolism Polyethylene Glycols / chemistry Polymers / chemistry, pharmacology* Zonula Occludens-1 Protein |
| Grant Support | |
ID/Acronym/Agency:
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5R01GM062344-11/GM/NIGMS NIH HHS; DK062719-22/DK/NIDDK NIH HHS; R01 GM062344-12/GM/NIGMS NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Bile Acids and Salts; 0/Membrane Proteins; 0/Phenols; 0/Phosphoproteins; 0/Polyethylene Glycols; 0/Polymers; 0/TJP1 protein, human; 0/Zonula Occludens-1 Protein; 83-44-3/Deoxycholic Acid; EC 3.4.22.-/Caspase 3; MLT3645I99/bisphenol A |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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