title: High crustacean toxicity of microcystin congeners does not correlate with high protein phosphatase inhibitory activity.
abstract: Microcystins are strong toxins and efficient inhibitors of eukaryotic protein phosphatases. To determine structure related properties of six different microcystin congeners, we applied standardized inhibition assays for the protein phosphatases 1 and 2A, and an acute toxicity assay with Thamnocephalus platyurus. Protein phosphatase inhibition and acute toxicity did not correlate with each other. While the inhibition of the protein phosphatases 1 and 2A was much weaker for [D-Asp3,(E)-Dhb7]microcystin-RR than for the other congeners, the toxicity was one of the highest. [D-Asp3]microcystin-LR exhibited only small differences to microcystin-LR. The data show that mechanisms other than the inhibition of protein phosphatases, such as uptake, transport, detoxification or other target sites may have a strong modulating effect on the toxicity of a microcystin congener for a particular animal. Structural changes can offset or even reverse the specific toxicity of microcystin congeners.
authors.affiliation: Limnological Station, Institute of Plant Biology, University of Zürich, Seestr. 187, 8802 Kilchberg, Switzerland. blom@limnol.unizh.ch
authors.forename: Judith F
authors.initials: JF
authors.lastname: Blom
authors.forename: Friedrich
authors.initials: F
authors.lastname: Jüttner
mesh_terms: D000818:Animals; D001427:Bacterial Toxins / Q000633:toxicity*; D003445:Crustacea / Q000187:drug effects*; D000458:Cyanobacteria / Q000737:chemistry*; D052998:Microcystins; D010456:Peptides, Cyclic / Q000633:toxicity*; D010749:Phosphoprotein Phosphatases / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship; D023382:Toxicity Tests, Acute / Q000379:methods
chemical_list: D001427:Bacterial Toxins; D052998:Microcystins; D010456:Peptides, Cyclic; C078588:microcystin; D010749:Phosphoprotein Phosphatases