Tài liệu Báo cáo khoa học: Marine toxins and the cytoskeleton: pectenotoxins, unusual macrolides

MINIREVIEW

Marine toxins and the cytoskeleton: pectenotoxins,

unusual macrolides that disrupt actin

Begon˜ a Espin˜ a1 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

The pectenotoxins (PTXs), macrolactones with multi￾ple polyether ring units that have been shown to con￾taminate shellfish in various parts of the world (Fig. 1)

[1–7], were first isolated from the Japanese scallop

Patinopecten yessoensis [8].

PTX-2 is produced by many species of the dinofla￾gellate genus Dinophysis, and it was initially detected

in Dinophysis fortii [9]. Later, this toxin was isolated

from Dinophysis acuminate, Dinophysis norvegica, Din￾ophysis rotundata and Dinophysis acuta [1–3,6,10–13].

After consumption of the algae by the shellfish, PTX-2

can be metabolized to other PTX derivatives. In the

digestive gland of the scallop P. yessoensis, the C43

methyl group in PTX-2 is oxidized to the alcohol

(PTX-1), aldehyde (PTX-3) and carboxylic acid (PTX￾6) forms [7,13]. Also, PTX-4 and PTX-7 have been

isolated from the digestive glands of scallops collected

in Japan, and these are stereoisomers of PTX-1 and

PTX-6, respectively. After acid treatment of PTX-4

and PTX-7, two isomers, named PTX-8 and PTX-9

respectively, were formed. These last two toxins are

not naturally occurring compounds, but artificial

toxins generated during isolation or acid treatment

[14]. On the other hand, in most bivalve species,

PTX-2 is metabolized to PTX-2 seco acid (PTX-2 SA),

in which the lactone ring of PTX-2 is hydrolyzed to

Keywords

actin cytoskeleton; biotoxins; cell line;

dinoflagellates; hepatotoxicity; macrolide;

mouse bioassay; pectenotoxin; primary

culture; red tide

Correspondence

B. Espin˜ a, Departamento de Farmacologı´a,

Facultad de Veterinaria, 27002 Lugo, Spain

Fax: +34 982 252 242

Tel: +34 982 252 242

E-mail: [email protected]

(Received 7 July 2008, revised 4 September

2008, accepted 8 September 2008)

doi:10.1111/j.1742-4658.2008.06714.x

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 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.

Intraperitoneal injection of pectenotoxins into mice produces high hepato￾toxicity as the principal symptom, so the liver seems to be their target

organ. Up to now, 15 pectenotoxin analogs have been discovered, with dif￾ferent 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.

Abbreviations

F-actin, filamentous actin; G-actin, globular actin; OA, okadaic acid; PTX, pectenotoxin; SA, seco acid.

6082 FEBS Journal 275 (2008) 6082–6088 ª 2008 The Authors Journal compilation ª 2008 FEBS