title: Low levels of selenium compounds are selectively toxic for a human neuron cell line through ROS/RNS increase and apoptotic process activation.
abstract: Organic and inorganic selenium compounds were used to examine whether low selenium concentration is able to trigger apoptotic degeneration in a human neuron cell line in vitro and to explore changes in reactive oxygen and nitrogen species and antioxidant protein content during the apoptotic processes. The results indicated that: (1) SKNBE neuroblastoma cells treated with sodium selenite, sodium selenate and seleno-methionine (0.1, 0.5 and 0.5 μM, respectively) for 24h exhibited a viability decrease, unlike kidney or prostatic cells; (2) the PARP (poly-ADP-ribose-polymerase) degradation and caspase activation detected by Western blot and flow cytometry fluorimetric examination showed induction of apoptosis; (3) during selenium treatment, a ROS/RNS increase occurred despite the GSH increment, as revealed by fluorimetric analysis; (4) the RNS production could be blocked by a peroxynitrite scavenger; (5) after exposure to selenium compounds, the concentration of nitric oxide synthase, manganese superoxide dismutase (SOD2), P-NF-kB (phospho nuclear factor kB), glutathione reductase and glutathione peroxidase increased, whereas that of P-ERK (phospho extracellular signal-regulated kinase) decreased; (6) selenium presence induced copper/zinc superoxide dismutase (SOD1) translocation into mitochondria, in a way similar to what is observed in amyotrophic lateral sclerosis (ALS). This study supports epidemiologic studies showing the possibility that excess environmental exposure to Se represents a risk factor for a devastating human neurodegenerative disease.
authors.affiliation: Department of Anatomy and Histology, University of Modena and Reggio Emilia, Via Del Pozzo 71, I-41100 Modena, Italy. tullia.maraldi@unimore.it
authors.forename: Tullia
authors.initials: T
authors.lastname: Maraldi
authors.forename: Massimo
authors.initials: M
authors.lastname: Riccio
authors.forename: Laura
authors.initials: L
authors.lastname: Zambonin
authors.forename: Marco
authors.initials: M
authors.lastname: Vinceti
authors.forename: Anto
authors.initials: A
authors.lastname: De Pol
authors.forename: Gabriele
authors.initials: G
authors.lastname: Hakim
mesh_terms: D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D006801:Humans; D009410:Nerve Degeneration / Q000139:chemically induced / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D018036:Selenium Compounds / Q000008:administration & dosage* / Q000633:toxicity*
chemical_list: D017382:Reactive Oxygen Species; D018036:Selenium Compounds