Marine toxins and the cytoskeleton: pectenotoxins, unusual macrolides that disrupt actin

Abstract

In recent years, many natural macrolactones have been found that display toxicity against the actin cytoskeleton. Pectenotoxins are macrolactones produced by species of the dinoflagellate genus Dinophysis. They were initially classified within the diarrheic shellfish poisoning group of toxins, because of their co‐occurrence and biological origin, but mice toxicity assays demonstrated that pectenotoxins do not induce diarrheic symptoms. Intraperitoneal injection of pectenotoxins into mice produces high hepatotoxicity as the principal symptom, so the liver seems to be their target organ. Up to now, 15 pectenotoxin analogs have been discovered, with different toxicological potencies that are related to their structures. Now, it is generally accepted that the actin cytoskeleton is the principal molecular target of pectenotoxins. Although recent studies have demonstrated that pectenotoxins induce actin filament disruption by a capping effect, other kinds of activity, such as sequestration of actin, cannot be ruled out. All of the active analogs tested triggered disruption of the actin cytoskeleton and displayed potencies that correlated with their toxicity in mice. Moreover, pectenotoxins induce apoptosis to a higher degree in tumor cells than in normal cells of the same tissue. This fact opens the prospect of studying new chemotherapy agents and actin cytoskeleton dynamics with potential clinical applications.

Quantitative proteomic analysis of okadaic acid treated mouse small intestines reveals differentially expressed proteins involved in diarrhetic shellfish poisoning

“…The microvilli are believed to increase cell surface area thus regulating the absorptive and secretory functions of epithelial cells. Recently, OA was proved to cause rapid changes in the structural organization of the intermediate filament, followed by a loss of microtubules, solubilization of intermediate filament proteins, and disruption of desmosomes [39][40][41]. So it is not surprising that a total of 11 cytoskeleton reorganization related proteins were altered after oral administration of OA and most of them were down-regulated.…”

Proteomic profile in Perna viridis after exposed to Prorocentrum lima, a dinoflagellate producing DSP toxins

“…Combined with down-regulation of annexins and actin-related protein 2, 3, we speculated that P. lima and associated DSP toxins might induce cytoskeletonal disorganization of mussel gills. Actually, OA-induced changes in cytoskeletal architecture and cellecell contact have been extensively reported (Leira et al, 2001;Espiña and Rubiolo, 2008;Vale and Botana, 2008;Vilariño et al, 2008;Espiña et al, 2010;Wang et al, 2011;Hanana et al, 2012;Huang et al, 2013;Opsahl et al, 2013). Using a mussel cDNA microarray, Manfrin et al (2010) found that 9% of up-regulated transcripts in mussel induced by OA exposure were potentially involved in cytoskeleton organization.…”

The methyl ester of okadaic acid is more potent than okadaic acid in disrupting the actin cytoskeleton and metabolism of primary cultured hepatocytes

“…However, the cells did not show the characteristic F-actin punctuated distribution, consequence of the treatment with other natural compounds that disorganize the actin cytoskeleton, for instance, pectenotoxins. These toxins disrupt the actin cytoskeleton of many kinds of cells, depolymerizing F-actin and preventing its polymerization (Ares et al, 2005;Ares et al, 2007;Espina and Rubiolo, 2008;. It is not clear yet if the extensive reorganization of the actin cytoskeleton induced by OA is a direct consequence of its activity or if it is an indirect consequence of the normal apoptotic process.…”