title: Cytotoxicity of yessotoxin and okadaic acid in mouse T lymphocyte cell line EL-4.
abstract: Yessotoxin (YTX) and okadaic acid (OA), algal toxins accumulated in edible shellfish, were previously shown to induce a specific and reversible T Cell Receptor (TCR) down-regulation in T lymphocyte EL-4 cells, in a time and concentration-dependent manner, via protein kinase C (PKC) and serine/threonine protein phosphatase 2A (PP2A) activities. In this study we have evaluated the development of other signs of toxicity induced by low concentrations of YTX or OA for 3 days of treatment. Concentrations of YTX as low as 1 nM decreased a 35% the concentration of viable cells after 48 h exposure to the toxin, while concentrations as little as 5 nM YTX or OA were sufficient to induce membrane blebbing. The concentration of YTX that produced after 24 h of incubation a 50% reduction in maximum cell viability (EC50₂₄) was approximately 46 nM, whereas with OA over 75% of the cells were still viable after exposure to 100 nM OA. According to our results, the cytoskeleton of EL-4 cells seems to be a cell component particularly sensitive to YTX and OA with disruption of F-actin cytoskeleton in these cells treated with concentrations of YTX or OA as low as 5 nM at 48 h incubation. Toxicity by YTX or OA involved typical hallmarks of apoptosis and an increase of reactive oxygen species (ROS) production. The cytotoxic effects of YTX and OA reported here, and the previously demonstrated potential of these toxins to regulate the activity of EL-4 cells through the regulation of TCR expression, rise reasonable concern about possible risks for human health associated to the chronic exposure to low amounts of YTX or OA itself or enhanced by the presence of other shellfish toxins specially by a population potentially at risk such as immunocompromised patients.
authors.affiliation: Department of Chemical Engineering, University of Almería, Crta. de Sacramento s/n, La Cañada, 04120 Almería, Spain. alicia@ual.es
authors.forename: Alicia
authors.initials: A
authors.lastname: Martín-López
authors.forename: Juan J
authors.initials: JJ
authors.lastname: Gallardo-Rodríguez
authors.forename: Asterio
authors.initials: A
authors.lastname: Sánchez-Mirón
authors.forename: Francisco
authors.initials: F
authors.lastname: García-Camacho
authors.forename: Emilio
authors.initials: E
authors.lastname: Molina-Grima
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D017304:Annexin A5 / Q000378:metabolism; D017209:Apoptosis; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D003599:Cytoskeleton / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008978:Mollusk Venoms; D019319:Okadaic Acid / Q000633:toxicity*; D035964:Oxocins / Q000633:toxicity*; D017382:Reactive Oxygen Species; D012758:Shellfish / Q000032:analysis; D013601:T-Lymphocytes / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology
chemical_list: D000199:Actins; D017304:Annexin A5; D008978:Mollusk Venoms; D035964:Oxocins; D017382:Reactive Oxygen Species; D019319:Okadaic Acid; C066632:yessotoxin