A novel cyanobacterial nostocyclopeptide is a potent antitoxin against microcystins.
Cyanobacterial hepatotoxins (microcystins and nodularins) cause numerous animal poisonings worldwide each year and are threats to human health. However, we found that extracts from several cyanobacteria isolates failed to induce hepatotoxicity even if they contained high concentrations of the liver toxin microcystin. The antitoxic activity abolishes all morphological hallmarks of microcystin-induced apoptosis, and therefore invalidates cell-based assays of the microcystin content of bloom-forming cyanobacteria. The antitoxin was purified from a cyanobacterial isolate (Nostoc sp. XSPORK 13A) from the Baltic Sea, and the activity was shown to reside in a novel cyclic peptide of the nostocyclopeptide family (nostocyclopeptide M1, Ncp-M1) that consists of seven amino acids (Tyr1-Tyr2-D-HSe3-L-Pro4-L-Val5-(2S,4S)-4-MPr6-Tyr7; MW=881) with an imino linkage between Tyr1 and Tyr7. Ncp-M1 did not compete with labelled microcystin for binding to protein phosphatase 2A; this explains why the antitoxin did not interfere with phosphatase-based microcystin assays. Currently used agents that interfere with microcystin action, such as inhibitors of ROS formation, microcystin uptake and Cam-kinase activity, are themselves inherently toxic. Since Ncp-M1 is potent and nontoxic it promises to become a useful mechanistic tool as soon as its exact cellular target is elucidated.
Jokela
Jouni
J
Department of Food and Environmental Sciences, Division of Microbiology, University of Helsinki, P. O. Box 56, 00014 Helsinki, Finland.
Herfindal
Lars
L
Wahlsten
Matti
M
Permi
Perttu
P
Selheim
Frode
F
Vasconçelos
Vitor
V
Døskeland
Stein Ove
SO
Sivonen
Kaarina
K
D000992:Antitoxins / Q000737:chemistry* / Q000302:isolation & purification; D002273:Carcinogens; D000458:Cyanobacteria / Q000737:chemistry*; D052998:Microcystins / Q000037:antagonists & inhibitors*; D010456:Peptides, Cyclic / Q000302:isolation & purification / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D000992:Antitoxins; D002273:Carcinogens; D052998:Microcystins; D010456:Peptides, Cyclic; C560265:nostocyclopeptide M1, Nostoc; C063998:nodularin