Toxicologic evaluation of Yessotoxin

Ogino, Hiroyuki; Kumagai, Masanori; Yasumoto, Takeshi

doi:10.1002/(sici)1522-7189(1997)5:6<255::aid-nt6>3.0.co;2-p

Cited by 162 publications

(79 citation statements)

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“…Animal studies indicate that PTXs and YTXs are much less toxic via the oral route and that they do not induce diarrhea. [13][14][15][16] PTXs and YTXs have recently been eliminated from the definition of DSP toxins. The mouse bioassay (MBA), which is the official testing method of DSP in Japan and many countries, also detects PTXs and YTXs, resulting in false positives for OA/DTX analogues.…”

Section: Introductionmentioning

confidence: 99%

LC-MS/MS Analysis of Diarrhetic Shellfish Poisoning (DSP) Toxins, Okadaic Acid and Dinophysistoxin Analogues, and Other Lipophilic Toxins

Suzuki

Quilliam

2011

ANAL. SCI.

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Section: Introductionmentioning

confidence: 99%

LC-MS/MS Analysis of Diarrhetic Shellfish Poisoning (DSP) Toxins, Okadaic Acid and Dinophysistoxin Analogues, and Other Lipophilic Toxins

Suzuki

Quilliam

2011

ANAL. SCI.

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“…These natural compounds are included among algal toxins because i.p. injection of yessotoxin into mice leads to death at doses as low as 80 mg kg À1 (Murata et al, 1987;Ciminiello et al, 1997;Ogino et al, 1997). As YTXs can be accumulated in edible molluscs, such as scallops and mussels (Murata et al, 1987;Ciminiello et al, 1997), by filter feeding, the current European legislation sets the limits of YTX contamination in material destined to human consumption (European Communities, 2002).…”

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confidence: 99%

Selective disruption of the E-cadherin–catenin system by an algal toxin

et al. 2004

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Yessotoxins (YTXs) are algal toxins that can be accumulated in edible molluscs. YTX treatment of MCF-7 breast cancer cells causes the accumulation of a 100 kDa fragment of E-cadherin, which we have named ECRA 100 . A relative decrease in the concentrations of intact E-cadherin did not accompany the accumulation of ECRA 100 in cytosoluble extracts of MCF-7 cells on the first day of YTX treatment, but a collapse of the E-cadherin system was detected after 2 -5 days of treatment with the toxin. An analysis of the general structure of ECRA 100 revealed that it consists of an E-cadherin fragment lacking the intracellular domain of the protein.ECRA 100 was not released into culture media of YTX-treated cells. Accumulation of ECRA 100 was observed in other epithelial cells, such as human intestine Caco-2 and MDCK cells after treatment with YTX. In turn, YTX could not induce accumulation of fragments of other members of the cadherin family, such as N-cadherin in the PC12 cell line and K-cadherin in sensitive cells (MCF-7, Caco-2, MDCK). The accumulation of a 100 kDa fragment of E-cadherin devoid of its intracellular domain induced by YTX was accompanied by reduced levels of b-and g-catenins bound to E-cadherin, without a concomitant decrease in the total cytosoluble pools of b-and g-catenins. Taken together, the results we obtained show that YTX causes the selective disruption of the E-cadherin -catenin system in epithelial cells, and raise some concern about the potential that an algal toxin found in seafood might disrupt the tumour suppressive functions of E-cadherin.

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“…Later, it was separated in its own group, due to different biological origin and different in vivo effects. 4 One of the main differences with OA is that YTX shows no inhibition of protein phosphatase 2A (PP2A). 5 Recently, it has been observed that, in fact, YTX and OA show an immunoregulatory effect over lymphocytes, although through protein kinase C (PKC) mediated mechanisms in the case of YTX and through PP2A mechanisms in the case of OA.…”

Section: −3mentioning

confidence: 99%

Translocation of PKC by Yessotoxin in an in Vitro Model of Alzheimer’s Disease with Improvement of Tau and β-Amyloid Pathology

Albrecht

Vale

Vieytes

et al. 2013

ACS Chem. Neurosci.

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Yessotoxin is a marine phycotoxin that induces motor alterations in mice after intraperitoneal injection. In primary cortical neurons, yessotoxin treatment induced a caspase-independent cell death with an IC 50 of 4.27 nM. This neurotoxicity was enhanced by 4,4′-diisothiocyanatostilbene-2,2′-disulfonic acid and partially blocked by amiloride. Unlike previous studies, yessotoxin did not increase cyclic adenosine monophosphate levels or produce any change in phosphodiesterase 4 steady state expression in triple transgenic neurons. Since phosphodiesterases (PDEs) are engaged in learning and memory, we studied the in vitro effect of the toxin against Alzheimer's disease hallmarks and observed that pretreatment of cortical 3xTg-AD neurons with a low nanomolar concentration of yessotoxin showed a decrease expression of hyperphosphorylated tau isoforms and intracellular accumulation of amyloid-beta. These effects were accompanied with an increase in the level of the inactive isoform of the glycogen synthase kinase 3 and also by a translocation of protein kinase C from cytosol to membrane, pointing to its activation. In fact, inhibition of protein kinase C with GF109203X blocked the effect of yessotoxin over tau protein. The data presented here shows that 1 nM yessotoxin activates protein kinase C with beneficial effects over the main Alzheimer's disease hallmarks, tau and Aβ, in a cellular model obtained from 3xTg-AD fetuses. KEYWORDS: Marine toxin, yessotoxin, Alzheimer's disease, protein kinase C Y essotoxin (YTX) is a marine phycotoxin with more than 40 analogues isolated for the first time in Japanese waters. It is produced by different dinoflagellates, among them, Protoceratium reticulatum and Lingulodinium polyedrum. 1−3Originally, the toxin was included with the okadaic acid (OA) in the group of diarrheic shellfish poisoning (DSP) toxins, because they used to appear together during toxic episodes. Later, it was separated in its own group, due to different biological origin and different in vivo effects. 4 One of the main differences with OA is that YTX shows no inhibition of protein phosphatase 2A (PP2A). 5 Recently, it has been observed that, in fact, YTX and OA show an immunoregulatory effect over lymphocytes, although through protein kinase C (PKC) mediated mechanisms in the case of YTX and through PP2A mechanisms in the case of OA. 6PKC is widely expressed in neurons, and it is implicated in neuroprotection, synaptic function, and plasticity. This turns it into an important molecule in learning and memory, and its signaling disruption causes impairment in these processes. 7−9Moreover, reduced PKC levels were found in samples from patients with Alzheimer's disease (AD).10 Several pieces of evidence indicate that amyloid beta (Aβ) peptide can reduce PKC levels and also block the activation and normal function of the enzyme.11 All these findings indicate that PKC activators may constitute an interesting target for AD related pathology, as PKC isoforms are involved in memory processing and the enzyme c...

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Toxicologic evaluation of Yessotoxin

Cited by 162 publications

References 1 publication

LC-MS/MS Analysis of Diarrhetic Shellfish Poisoning (DSP) Toxins, Okadaic Acid and Dinophysistoxin Analogues, and Other Lipophilic Toxins

LC-MS/MS Analysis of Diarrhetic Shellfish Poisoning (DSP) Toxins, Okadaic Acid and Dinophysistoxin Analogues, and Other Lipophilic Toxins

Selective disruption of the E-cadherin–catenin system by an algal toxin

Translocation of PKC by Yessotoxin in an in Vitro Model of Alzheimer’s Disease with Improvement of Tau and β-Amyloid Pathology

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