RT Journal Article T1 Enniatins A1 and B1 alter calcium homeostasis of neuronal cells leading to apoptotic death A1 Pérez Fuentes, Nadia A1 Alvariño Romero, Rebeca A1 Alfonso Rancaño, María Amparo A1 González Jartín, Jesús María A1 Gegunde Mosquera, Sandra A1 Rodríguez Vieytes, Mercedes A1 Botana López, Luis Miguel K1 Enniatins K1 Calcium fluxes K1 Apoptosis K1 Mitochondria K1 Combined toxicity AB Enniatins (ENNs) A1 and B1 are non-regulated mycotoxins produced by Fusarium spp. that commonly occur in different types of food. These toxins are cytotoxic in several cell lines, but their mechanism of action is unclear. In this study, the cytotoxic effects of ENNs A1 and B1 in SH-SY5Y human neuroblastoma cells were analysed. Moreover, to better understand their mechanism of action, mitochondrial function, reactive oxygen species (ROS) levels and calcium fluxes were monitored. ENNs A1 and B1 reduced cell viability, presenting IC50 values of 2.0 and 2.7 μM, respectively. Both toxins induced caspase-dependent apoptosis, but only ENN A1 increased ROS production. Apoptotic cell death seems to be triggered by the increase in cytosolic calcium produced by both ENNs, since the toxins altered Ca2+ homeostasis by depleting intracellular reservoirs. Finally, binary combinations of ENN A1, ENN B1, ENN A and ENN B were tested. All mixtures resulted in an antagonistic effect, with the exception of ENN A and ENN B1 combination, which produced an additive effect. The results presented in this study provide the first evidence of ENNs A1 and B1 effects on calcium fluxes, providing new insights into the mechanism of action of these mycotoxins PB Elsevier YR 2022 FD 2022 LK http://hdl.handle.net/10347/29461 UL http://hdl.handle.net/10347/29461 LA eng NO Food and Chemical Toxicology 168 (2022) 113361 NO The research leading to these results has received funding from the following FEDER cofunded-grants. From Conselleria de Cultura, Educacion e Ordenación Universitaria, Xunta de Galicia, GRC (ED431C 2021/01). From Ministerio de Ciencia e Innovación IISCIII/PI19/001248 and PID 2020-11262RB-C21. From European Union Interreg Agritox EAPA-998-2018, and H2020 778069-EMERTOX. R. Alvariño is supported by a postdoctoral fellowship from Xunta de Galicia (ED481B-2021-038), Spain. N.P–F. is supported by a fellowship from FIDIS, Spain DS Minerva RD 29 abr 2026