Microcystin-LR and okadaic acid-induced cellular effects: a dualistic response.
Microcystins, potent heptapeptide hepatotoxins produced by certain bloom-forming cyanobacteria, are strong protein phosphatase inhibitors. They covalently bind the serine/threonine protein phosphatases 1 and 2A (PP1 and PP2A), thereby influencing regulation of cellular protein phosphorylation. The paralytic shellfish poison, okadaic acid, is also a potent inhibitor of these PPs. Inhibition of PP1 and PP2A has a dualistic effect on cells exposed to okadaic acid or microcystin-LR, with both apoptosis and increased cellular proliferation being reported. This review summarises the existing data on the molecular effects of microcystin-LR inhibition of PP1 and PP2A both in vivo and in vitro, and where possible, compares this to the action of okadaic acid.
Gehringer
Michelle M
MM
School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, NSW 2052, Australia. mgehringer@unsw.edu.au
D000818:Animals; D000970:Antineoplastic Agents / Q000633:toxicity; D017209:Apoptosis / Q000187:drug effects; D001427:Bacterial Toxins / Q000633:toxicity*; D002455:Cell Division / Q000187:drug effects; D003599:Cytoskeleton / Q000187:drug effects / Q000648:ultrastructure; D004791:Enzyme Inhibitors / Q000633:toxicity*; D006801:Humans; D008387:Marine Toxins; D052998:Microcystins; D019319:Okadaic Acid / Q000633:toxicity*; D010456:Peptides, Cyclic / Q000633:toxicity*; D010749:Phosphoprotein Phosphatases / Q000037:antagonists & inhibitors*
D000970:Antineoplastic Agents; D001427:Bacterial Toxins; D004791:Enzyme Inhibitors; D008387:Marine Toxins; D052998:Microcystins; D010456:Peptides, Cyclic; D019319:Okadaic Acid; D010749:Phosphoprotein Phosphatases; C057862:cyanoginosin LR