Increased susceptibility to oxidative stress in scrapie-infected neuroblastoma cells is associated with intracellular iron status.
The molecular mechanism of neurodegeneration in prion diseases remains largely uncertain, but one of the features of infected cells is higher sensitivity to induced oxidative stress. In this study, we have investigated the role of iron in hydrogen peroxide (H(2)O(2))-induced toxicity in scrapie-infected mouse neuroblastoma N2a (ScN 2 a) cells. ScN 2 a cells were significantly more susceptible to H(2)O(2) toxicity than N2a cells as revealed by cell viability (MTT) assay. After 2h exposure, significant decrease in cell viability in ScN 2 a cells was observed at low concentrations of extracellular H(2)O(2) (5-10 microM), whereas N2a cells were not affected. The increased H(2)O(2) toxicity in ScN 2 a cells may be related to intracellular iron status since ferrous iron (Fe(2+)) chelator 2,2'-bipyridyl (BIP) prevented H(2)O(2)-induced decrease in cell viability. Further, the level of calcein-sensitive labile iron pool (LIP) was significantly increased in ScN 2 a cells after H(2)O(2) treatment. Finally, the production of reactive oxygen species (ROS) was inhibited by 30% by iron chelators desferrioxamine (DFO) and BIP in ScN 2 a cells, whereas no significant effect of iron chelators on basal ROS production was observed in N2a cells. This study indicates that cellular resistance to oxidative stress in ScN 2 a cells is associated with intracellular status of reactive iron.
Fernaeus
Sandra
S
Department of Neurochemistry, Stockholm University, S-106 91 Stockholm, Sweden. sandra@neurochem.su.se
Reis
Katarina
K
Bedecs
Katarina
K
Land
Tiit
T
D000818:Animals; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004198:Disease Susceptibility / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D007424:Intracellular Fluid / Q000378:metabolism*; D007501:Iron / Q000378:metabolism*; D051379:Mice; D009447:Neuroblastoma / Q000378:metabolism* / Q000821:virology; D018384:Oxidative Stress / Q000187:drug effects*; D012608:Scrapie / Q000378:metabolism*
D006861:Hydrogen Peroxide; D007501:Iron