Document Detail

Mitochondrial toxicity of microcystin-LR on cultured cells: application to the analysis of contaminated water samples.
MedLine Citation:
PMID:  20192251     Owner:  NLM     Status:  MEDLINE    
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.
Grzegorz Jasionek; Alexander Zhdanov; John Davenport; Ludek Bl?ha; Dimitri B Papkovsky
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Environmental science & technology     Volume:  44     ISSN:  0013-936X     ISO Abbreviation:  Environ. Sci. Technol.     Publication Date:  2010 Apr 
Date Detail:
Created Date:  2010-03-30     Completed Date:  2010-06-07     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0213155     Medline TA:  Environ Sci Technol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2535-41     Citation Subset:  IM    
Biochemistry Department, University College Cork, College Road, Cork, Ireland.
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MeSH Terms
Acids / metabolism
Biological Transport / drug effects
Cells, Cultured
Extracellular Space / drug effects,  metabolism
Hep G2 Cells
Hepatocytes / drug effects,  metabolism
Jurkat Cells
Luminescent Agents / metabolism
Microcystins / toxicity*
Mitochondria, Liver / drug effects*,  metabolism
Oxygen Consumption / drug effects
Rats, Sprague-Dawley
Water Pollution / analysis*
Reg. No./Substance:
0/Acids; 0/Luminescent Agents; 0/Microcystins; 101043-37-2/cyanoginosin LR

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