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Microcystin congener- and concentration-dependent induction of murine neuron apoptosis and neurite degeneration.
MedLine Citation:
PMID:  21934130     Owner:  NLM     Status:  Publisher    
Cyanobacterial microcystins (MCs) represent a toxin group with >100 variants, requiring active uptake into cells via organic anion transporting polypeptides, in order to irreversibly inhibit serine/threonine-specific protein phosphatases. MCs are a human health hazard with repeated occurrences of severe poisonings. In the well known human MC intoxication in Caruaru, Brazil (1996) patients developed signs of acute neurotoxicity, e.g. deafness, tinnitus and intermittent blindness, as well as subsequent hepatotoxicity. The latter data, in conjunction with some animal studies, suggest that MCs are potent neurotoxins. However, there is little data to date demonstrating MC neuron-specific toxicity. This study examined the neurotoxicity of MC-LR, MC-LW and MC-LF in primary murine cerebellar granule neurons. MC exposure induced cytotoxicity, caspase activity, chromatin condensation and microtubule associated Tau protein hyperphosphorylation (epitopes serine199/202 and serine396) was determined. Neurite degeneration was analyzed with confocal microscopy and neurite length determined using image analysis. MC induced apoptosis was significantly increased by MC-LF and MC-LW, however only at high concentrations (≥3μM), whereas significant neurite degeneration was already observed at 0.5 μM MC-LF. Moreover, sustained hyperphosphorylation of Tau was observed with all MC congeners. The concentration- and congener-dependent mechanisms observed suggest that low concentrations of MC-LF and MC-LW can induce subtle neurodegenerative effects, reminiscent of Alzheimer's disease type human tauopathies, and thus should be taken more seriously with regard to potential human health effects than the apical cytotoxicity (apoptosis or necrosis) demonstrated at high MC concentrations.
Daniel Feurstein; Kerstin Stemmer; Julia Kleinteich; Tobias Speicher; Daniel R Dietrich
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-9-20
Journal Detail:
Title:  Toxicological sciences : an official journal of the Society of Toxicology     Volume:  -     ISSN:  1096-0929     ISO Abbreviation:  -     Publication Date:  2011 Sep 
Date Detail:
Created Date:  2011-9-21     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9805461     Medline TA:  Toxicol Sci     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Human and Environmental Toxicology, University of Konstanz, Konstanz, Germany.
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