High crustacean toxicity of microcystin congeners does not correlate with high protein phosphatase inhibitory activity.
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.
Blom
Judith F
JF
Limnological Station, Institute of Plant Biology, University of Zürich, Seestr. 187, 8802 Kilchberg, Switzerland. blom@limnol.unizh.ch
Jüttner
Friedrich
F
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
D001427:Bacterial Toxins; D052998:Microcystins; D010456:Peptides, Cyclic; C078588:microcystin; D010749:Phosphoprotein Phosphatases