Low levels of selenium compounds are selectively toxic for a human neuron cell line through ROS/RNS increase and apoptotic process activation

Organic and inorganic selenium compounds were used to examinewhether low selenium concentrationis able to trigger apoptotic degeneration in a human neuron cell line in vitro and to explore changes inreactive 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 selenateand seleno-methionine (0.1, 0.5 and 0.5 mM, respectively) for 24 h exhibited a viability decrease, unlikekidney or prostatic cells; (2) the PARP (poly-ADP-ribose-polymerase) degradation and caspase activationdetected 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 byfluorimetric analysis; (4) the RNS production could be blocked by a peroxynitrite scavenger; (5) afterexposure to selenium compounds, the concentration of nitric oxide synthase, manganese superoxidedismutase (SOD2), P-NF-kB (phospho nuclear factor kB), glutathione reductase and glutathioneperoxidase 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 supportsepidemiologic studies showing the possibility that excess environmental exposure to Se represents a riskfactor for a devastating human neurodegenerative disease.