| Mitochondrial toxicity of microcystin-LR on cultured cells: application to the analysis of contaminated water samples. | |
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MedLine Citation:
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PMID: 20192251 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Microcystins (MC) are potent hepatic toxins delivered into the cells by organic anion transporting peptides (OATP) where they target protein phosphatases and mitochondria. We analyzed the effects of MC-LR on primary hepatocytes, HepG2, and Jurkat T cells, and isolated rat liver mitochondria by measuring changes in O(2) consumption by optical oxygen sensing technique. Respiration of fresh primary hepatocytes was inhibited by MC-LR with EC50 = 2.74 +/- 0.65 nM, whereas an uncoupling effect on mitochondrial state 2 and state 3 respiration was observed with glutamate/malate as a substrate. HepG2 and Jurkat T cells lacking OATP showed no sensitivity to MC-LR; however, facilitated delivery of MC-LR resulted in a marked enhancement of HepG2 O(2) consumption and inhibition of Jurkat O(2) consumption at >or=0.1 nM. The respiratory response did not coincide with changes in viability, total cellular ATP, extracellular acidification, ROS formation, or protein phosphorylation, which were detectable at higher MC-LR doses. Such prominent effect on cellular respiration was therefore used for the detection of MC-LR in environmental samples. A simple and sensitive screening assay for MC-LR toxicity was developed, which uses Jurkat cells, facilitated delivery of the toxin(s) and measurement on a fluorescent reader. The assay was applied to a panel of environmental samples suspected to contain MC and benchmarked against the ELISA test. It allowed identification of toxic samples and quantification of both nonspecific and MC-LR type of toxicity. |
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Authors:
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Grzegorz Jasionek; Alexander Zhdanov; John Davenport; Ludek Bl?ha; Dimitri B Papkovsky |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Environmental science & technology Volume: 44 ISSN: 0013-936X ISO Abbreviation: Environ. Sci. Technol. Publication Date: 2010 Apr |
Date Detail:
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Created Date: 2010-03-30 Completed Date: 2010-06-07 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0213155 Medline TA: Environ Sci Technol Country: United States |
Other Details:
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Languages: eng Pagination: 2535-41 Citation Subset: IM |
Affiliation:
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Biochemistry Department, University College Cork, College Road, Cork, Ireland. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Acids
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metabolism Animals Biological Transport / drug effects Cells, Cultured Environment Extracellular Space / drug effects, metabolism Hep G2 Cells Hepatocytes / drug effects, metabolism Humans Jurkat Cells Luminescent Agents / metabolism Male Microcystins / toxicity* Mitochondria, Liver / drug effects*, metabolism Oxygen Consumption / drug effects Rats Rats, Sprague-Dawley Water Pollution / analysis* |
| Chemical | |
Reg. No./Substance:
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0/Acids; 0/Luminescent Agents; 0/Microcystins; 101043-37-2/cyanoginosin LR |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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