Microcystin‐LR and okadaic acid‐induced cellular effects: a dualistic response

Abstract

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 in£uencing regulation of cellular protein phosphorylation. The paralytic shell¢sh poison, okadaic acid, is also a potent inhibitor of these PPs. Inhibition of PP1 and PP2A has a dualistic e¡ect 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 e¡ects 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.

Modulation of extracellular matrix protein phosphorylation alters mineralization in differentiating chick limb-bud mesenchymal cell micromass cultures

“…The CK2 antibody was from Santa Cruz Biotechnologies Inc (Santa Cruz, CA). The phosphatase inhibitors [27] that were used were okadaic acid (OA) and its inert form (okadaic acid tetraacetate), calyculin A, microcystin-LR, a bacteria derived phosphatase inhibitor that does not penetrate cell membranes [28], sodium vanadate, and levamisole or its inert form tetramisole. The two casein kinase II inhibitors used were apigenin and casein kinase II-inhibitor II (Calbiochem, La Jolla, CA).…”

Mitochondrial electron transport chain is involved in microcystin-RR induced tobacco BY-2 cells apoptosis

“…Chen et al (2009) identified that oxidative stress activates the MAPK pathway by induction of ROS and inhibition of PP 2A leading to apoptosis of neuronal cells. MC-RR can strongly inhibit PP 1 and PP 2A (Gehringer, 2004). Thereby it may be reasonable to speculate that MC-RR-induced apoptosis is in part through inhibition of PPs and induction of ROS, resulting in activation of MAPK signaling pathway.…”

“…The generally accepted noxious mechanism of MCs is the inhibition of protein phosphatase (PP) type-1 and 2A. MCs can covalently bind the PP 1 and 2A, thereby influencing regulation of balance between cellular protein phosphorylation and dephosphorylation (Gehringer, 2004). It is thought that MCs affect hepatocellular viability through induction of changes in the cytoskeleton triggered by inhibition of the PPs (Eriksson et al, 1989) and partially through generation of reactive oxygen species (ROS) (Ding et al, 2001).…”

Identification and expression profile of Id1 in bighead carp in response to microcystin-LR

“…Id1 also promotes invasion of cancer cells through regulating MMP protein as well as invasion (Fong et al, 2003). Animals usually show the dualistic response to MCLR exposure (Gehringer, 2004), cell apoptosis is generally reported at high doses of MCLR both in vivo and in vitro, and increased cellular proliferation is observed at lower concentrations. When bighead carps were injected with 200 g MCLR/kg bw, Id1 expression increased with time extension of MCLR exposure, and this is similar to MCLR toxic effect reported in other published papers (Gehringer, 2004).…”

“…Animals usually show the dualistic response to MCLR exposure (Gehringer, 2004), cell apoptosis is generally reported at high doses of MCLR both in vivo and in vitro, and increased cellular proliferation is observed at lower concentrations. When bighead carps were injected with 200 g MCLR/kg bw, Id1 expression increased with time extension of MCLR exposure, and this is similar to MCLR toxic effect reported in other published papers (Gehringer, 2004). While in heart the upregulation of Id1 expression at 3 h is much more than at 24 h. Maybe at 3 h the dose of MCLR accumulated in heart was low so cells in heart were promoted to proliferation and Id1 expression was at a high level, when at 24 h post MCLR exposure, no MCLR existed in heart according to Lei et al (2008), so no toxin to promote cell proliferation and Id1expression decreased when detected at this time.…”