| Esterification prevents induction of the mitochondrial permeability transition by N-acetyl perfluorooctane sulfonamides. | |
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MedLine Citation:
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PMID: 17040099 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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N-Alkyl perfluorooctane sulfonamides have been widely used as surfactants on fabrics and papers, fire retardants, and anticorrosion agents, among many other commercial applications. The broad use, global distribution, and environmental persistence of these compounds has generated considerable interest regarding potentially toxic effects. We have previously reported that perfluorooctanesulfonamidoacetate (FOSAA) and N-ethylperfluorooctanesulfonamidoacetate (N-EtFOSAA) induce the mitochondrial permeability transition (MPT) in vitro, resulting in cytochrome c release, inhibition of respiration, and generation of reactive oxygen species. By synthesizing the corresponding methyl esters of FOSAA and N-EtFOSAA (methyl perlfuorinated sulfonamide acetates), we tested the hypothesis that the N-acetate moiety of FOSAA and N-EtFOSAA is the functional group responsible for induction of the MPT. Swelling of freshly isolated liver mitochondria from Sprague-Dawley rats was monitored spectrophotometrically and membrane potential (DeltaPsi) was measured using a tetraphenylphosphonium-selective (TPP(+)) electrode. In the presence of calcium, 40 microM FOSAA and 7 microM N-EtFOSAA each induced mitochondrial swelling and a biphasic depolarization of membrane potential. Mitochondrial swelling and the second-phase depolarization were inhibited by cyclosporin-A or the catalyst of K(+)/H(+) exchange nigericin, whereas the first-phase depolarization was not affected by either. In contrast, the methyl esters of FOSAA and N-EtFOSAA exhibited no depolarizing or MPT inducing activity. Results of this investigation demonstrate that the carboxylic acid moiety of the N-acetates is the active functional group, which triggers the MPT by perfluorinated sulfonamides. |
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Authors:
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Timothy M O'Brien; Robert M Carlson; Paulo J Oliveira; Kendall B Wallace |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Chemical research in toxicology Volume: 19 ISSN: 0893-228X ISO Abbreviation: Chem. Res. Toxicol. Publication Date: 2006 Oct |
Date Detail:
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Created Date: 2006-10-16 Completed Date: 2007-02-08 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8807448 Medline TA: Chem Res Toxicol Country: United States |
Other Details:
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Languages: eng Pagination: 1305-12 Citation Subset: IM |
Affiliation:
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Department of Biochemistry and Molecular Biology, Toxicology Graduate Program, University of Minnesota, Medical School, 1035 University Drive, Duluth, Minnesota 55812, USA. obri0150@d.uuumn.edu |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Calcium / chemistry, pharmacology Esterification Female Fluorocarbons / chemistry* Male Membrane Potential, Mitochondrial / drug effects Mitochondrial Membranes / drug effects* Mitochondrial Swelling / drug effects Molecular Structure Permeability / drug effects Rats Rats, Sprague-Dawley Sulfonamides / chemistry*, pharmacology* Titrimetry |
| Chemical | |
Reg. No./Substance:
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0/Fluorocarbons; 0/Sulfonamides; 7440-70-2/Calcium |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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