TAILIEUCHUNG - Báo cáo khoa học: Marine toxins and the cytoskeleton: pectenotoxins, unusual macrolides that disrupt actin

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 genusDinophysis. They were ini-tially 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. | MINIREVIEW Marine toxins and the cytoskeleton pectenotoxins unusual macrolides that disrupt actin Begona Espina1 and Juan A. Rubiolo1 2 1 Departamento de Farmacologia Facultad de Veterinaria Universidad de Santiago de Compostela Lugo Spain 2 Departamento de Fisiologia Animal Facultad de Veterinaria Universidad de Santiago de Compostela Lugo Spain Keywords actin cytoskeleton biotoxins cell line dinoflagellates hepatotoxicity macrolide mouse bioassay pectenotoxin primary culture red tide Correspondence B. Espina Departamento de Farmacologia Facultad de Veterinaria 27002 Lugo Spain Fax 34 982 252 242 Tel 34 982 252 242 E-mail Received 7 July 2008 revised 4 September 2008 accepted 8 September 2008 doi 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 .

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