A Novel Cyanobacterial Nostocyclopeptide is a Potent Antitoxin against Microcystins

• Type: Article in International Scientific Journal
• Date: 2010

Authors

Jouni Jokela (Author) Other; Lars Herfindal (Author) Other; Matti Wahlsten (Author) Other; Perttu Permi (Author) Other; Frode Selheim (Author) Other; Vitor Vasconçelos (Author) Other; Stein Ove Dÿskeland (Author) Other; Kaarina Sivonen (Author) Other

Journal

Title: ChemBioChem

Vol. 11

Pages: 1594-1599

ISSN: 1439-4227

Publisher: Wiley-Blackwell

Indexing

ISI Web of Knowledge - 36 Citations

Scopus - 41 Citations

Other information

Authenticus ID: P-003-4QJ

DOI: 10.1002/cbic.201000179

Abstract (EN): 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 (Tyr(1)-Tyr(2)-D-HSe(3)-L-Pro(4)-L-Val(5)-(2S,4S)-4-MPr(6)-Tyr(7); M(W) = 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.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 6