title: Protein synthesis inhibition and oxidative stress induced by cylindrospermopsin elicit apoptosis in primary rat hepatocytes.
abstract: The increasing presence of cyanotoxin producers in several regions of the world is hazardous for humans and animals. Cylindrospermopsin (CYN) is nowadays recognized as a widely distributed freshwater cyanobacterial toxin. This toxin has been shown to induce protein synthesis inhibition as well as inhibition of glutathione synthesis. Given that the liver seems to be the main target of cylindrospermopsin, in this work we used cultures of primary rat hepatocytes to study the type of cell death induced by CYN nanomolar concentrations. The involvement of reactive oxygen species in toxin induced cell death, the relationship between protein synthesis inhibition and toxicity, and the cell endogenous antioxidant response regulation were studied. We show that cylindrospermopsin induces apoptosis in primary rat hepatocytes. At the concentrations used in this work, protein synthesis inhibition and oxidative stress were involved in the cytotoxic effect elicited by the toxin. Finally, activation of the cell antioxidant response was observed at the transcriptional and translational levels.
authors.affiliation: Departamento de Farmacología, Fac. Veterinaria, Universidad de Santiago de Compostela, 27002 Lugo, Spain.
authors.forename: Henar
authors.initials: H
authors.lastname: López-Alonso
authors.forename: Juan Andrés
authors.initials: JA
authors.lastname: Rubiolo
authors.forename: Félix
authors.initials: F
authors.lastname: Vega
authors.forename: Mercedes R
authors.initials: MR
authors.lastname: Vieytes
authors.forename: Luis M
authors.initials: LM
authors.lastname: Botana
mesh_terms: D000470:Alkaloids; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects*; D001427:Bacterial Toxins / Q000633:toxicity*; D002478:Cells, Cultured; D000458:Cyanobacteria / Q000737:chemistry; D000087522:Cyanobacteria Toxins; D022781:Hepatocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008387:Marine Toxins / Q000633:toxicity*; D052998:Microcystins / Q000633:toxicity*; D018384:Oxidative Stress / Q000187:drug effects*; D014176:Protein Biosynthesis / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D014498:Uracil / Q000031:analogs & derivatives* / Q000633:toxicity
chemical_list: D000470:Alkaloids; D000975:Antioxidants; D001427:Bacterial Toxins; D000087522:Cyanobacteria Toxins; D008387:Marine Toxins; D052998:Microcystins; C089595:cylindrospermopsin; D014498:Uracil