Feasibility of gymnodimine and 13-desmethyl C spirolide detection by fluorescence polarization using a receptor-based assay in shellfish matrixes

Fonfría, Eva S.; Vilariño, Natalia; Espiña, Begoña; Louzao, M. Carmen; Alvarez, Mercedes; Molgó, Jordi; Aráoz, Rómulo; Botana, Luís M.

doi:10.1016/j.aca.2009.10.027

Cited by 38 publications

(25 citation statements)

References 21 publications

(25 reference statements)

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“…Although the exact mechanism of this neuroprotective effect was not identified, chronic treatment of cortical neurons with the toxin did not modify the glutamate-induced calcium response. Since nAchRs are the main target of gymnodimine and the toxin is an antagonist of these receptors [2,3,45], we explored whether the interaction between GYM and AchRs could have a relationship with the beneficial effect of the toxin against glutamate-induced neurotoxicity. Previous reports have shown that α7nAchR can protect against Aβ and glutamate induced neurotoxicity [7].…”

Section: Discussionmentioning

confidence: 99%

The Cholinergic Antagonist Gymnodimine Improves Aβ and Tau Neuropathology in an <i>in Vitro</i> Model of Alzheimer Disease

Albrecht¹,

Vale²,

Vieytes³

et al. 2011

Cell Physiol Biochem

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Gymnodimine (GYM) is a marine phycotoxin with a macrocyclic imine structure, isolated from extracts of the dinoflagellate Karenia selliformis known to act as a cholinergic antagonist with subtype selectivity. However, no data on the chronic effects of this compound has been reported so far. In this work, we evaluated the effect of long term exposure of cortical neurons to gymnodimine in the progress of Alzheimer disease (AD) pathology in vitro. Treatment of cortical neurons with 50 nM gymnodimine decreased the intracellular amyloid beta (Aβ) accumulation and the levels of the hyperphosphorylated isoforms of tau protein recognized by AT8 and AT100 antibodies. These results are suggested to be mediated by the increase in the inactive isoform of the glycogen synthase kinase-3 (phospho GSK-3 Ser9), the decrease in the levels of the active isoform of the ERK1/2 kinase and the increase in acetylcholine (Ach) synthesis elicited by long term exposure of cortical neurons to the toxin. Moreover, gymnodimine decreased glutamate-induced neurotoxicity in vitro. Altogether these results indicate that the marine phycotoxin gymnodimine may constitute a valuable tool for the development of drugs to treat neurodegenerative diseases.

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Section: Discussionmentioning

confidence: 99%

The Cholinergic Antagonist Gymnodimine Improves Aβ and Tau Neuropathology in an <i>in Vitro</i> Model of Alzheimer Disease

Albrecht¹,

Vale²,

Vieytes³

et al. 2011

Cell Physiol Biochem

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“…The method to quantify the PLTX is based on the FP methodology. In several studies, the FP technology was used to quantify toxins [29,32,33] and recently it was applied to develop a sensitive PLTX detection method [28]. In general, the FP units of a Na,K-ATPase-F conjugate decreased in the presence of PLTX and/or PLTX-like compounds with the same mechanism of action.…”

Section: Resultsmentioning

confidence: 99%

Warm Seawater Microalgae: Growth and Toxic Profile of Ostreopsis Spp. from European Coasts

Fernández-Araujo¹,

Alfonso²,

Antelo³

et al. 2013

Oceanography

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“…The aforementioned suggestion has been confirmed via binding of 13-desmethyl SPX C and GYM A to nAChRs in binding assays and voltage-clamp recordings on muscle and neuronal nAChR, hence revealing potent antagonism for both types of receptors (Bourne et al 2010). Nevertheless, the main difference between GYMs and SPXs is that GYMs show a reversible effect, whereas binding of SPXs seem to be irreversible (Molgó et al 2007, 2008, Fonfria et al 2010. Furthermore, the fact that SPXs containing an extra methyl group on the imine ring survive enzymatic hydrolysis conditions in shellfish implies that they might be toxic to humans, as well .…”

Section: Journal Of the Hellenic Veterinary Medical Society 201162(3)mentioning

confidence: 99%

“…It is based on the high affinity of GYM A and 13-desmethyl SPX C for the nicotinic acetylcholine receptor (nAChR) of the electric organ of the ray Torpedo marmorata, and their competition for binding to this receptor with abungarotoxin, which is fluorescently labelled ). The method's limit of quantification (LOQ) is 80 μg/kg for GYM A and 85 μg/kg for 13-desmethyl SPX C in shellfish (Fonfria et al 2010). This method is easy, fast, inexpensive and it detects any CIanalogue that may interact with nAChR.…”

Section: Biochemical Assaysmentioning

confidence: 99%

Cyclic imines, as emerging marine toxins: Chemical properties, distribution, toxicological aspects and detection methods

Chatzianastasiou¹,

Katikou²,

Zacharaki³

et al. 2017

J Hellenic Vet Med Soc

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Shellfish and, specifically, bivalve molluscs are a food commodity of great nterest for both commercial and public health reasons. They consume microalgae from surrounding waters, which are generally beneficial for aquaculture, but they comprise certain toxin-producing species. These species produce marine toxins which, via the filter-feeding mechanism of bivalve molluscs, accumulate in their tissues. This accumulation is more intense andmore dangerous for public health during the so-called periods of Harmful Algal Blooms (HABs) when the microalgal population grows. According to their chemical structure, marine toxins are classified into 8 groups, one of which is the cyclic imines. These lipophilic toxins were accidentally discovered during routine bioassays for the detection of other lipophilic marine toxins due to the induction of neurological symptoms and acute death in mice. They include the following subgroups: Spirolides (SPX), gymnodimines (GYM), pinnatoxins (PnTX), pteriatoxins (PtTX), prorocentrolides and spiro-prorocentrimines. The European Union (EU) is more concerned about the first three subgroups, because, in contrast with the latter three, they have already been detected in Europe or there is strong evidence supporting their presence. Spirolides are produced by the dmof\a.ge\\ate Alexandrìum ostenfeldii/peruvianum, gymnodimines by the dinoflagellate Karenia selliformis and pinnatoxins by a peridinoid dinoflagellate recently described in the new genus Vulcanodinium spp.. Although there is insufficient information regarding the geographical distribution of cyclic imines, the fact that they have been detected on multiple occasions in European waters, in combination with their aforementioned acute toxicity in mice after intraperitoneal injection, has established them, at least within the EU, as a topic of profound scientific research. In spite of their acute toxicity in mice, no incident of human intoxication has been attributed to cyclic imines. Presently, the EU has neither set any Maximum Permissible Limits for the concentration of cyclic imines in shellfish nor appointed any reference method for their detection and quantification. Currently, the methods applied are biological, biochemical and chemical. The biological method is a bioassay, which is conducted via the intraperitoneal injection of mice with an extract containing the compound under examination and it detects total toxicity. This properly is essential for the detection of unknown toxins, but the use of laboratory animals raises serious ethical concerns and animal welfare issues. The biochemical method is based on competition between cyclic imines and a fluorescently labelled compound for binding to receptors of the electric ray Torpedo marmorata. Finally, in respect of chemical methods, liquid chromatography with tandem mass spectrometry detection (LC-MS/MS) is the most significant method because it is fast, of high repeatability and specificity.

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Feasibility of gymnodimine and 13-desmethyl C spirolide detection by fluorescence polarization using a receptor-based assay in shellfish matrixes

Cited by 38 publications

References 21 publications

The Cholinergic Antagonist Gymnodimine Improves Aβ and Tau Neuropathology in an <i>in Vitro</i> Model of Alzheimer Disease

The Cholinergic Antagonist Gymnodimine Improves Aβ and Tau Neuropathology in an <i>in Vitro</i> Model of Alzheimer Disease

Warm Seawater Microalgae: Growth and Toxic Profile of Ostreopsis Spp. from European Coasts

Cyclic imines, as emerging marine toxins: Chemical properties, distribution, toxicological aspects and detection methods

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