title: Chemical nanotherapy: nitroxyl radical-containing nanoparticle protects neuroblastoma SH-SY5Y cells from Abeta-induced oxidative stress.
abstract: BACKGROUND
  Excessive accumulation of beta-amyloid (Abeta) has been proposed as a pivotal event in the pathogenesis of Alzheimer's disease. Possible mechanisms underlying Abeta-induced neuronal cytotoxicity include excess production of reactive oxygen species (ROS) and apoptosis. We have designed novel nanoparticles, nitroxyl radical-containing nanoparticles (RNPs), which possess nitroxyl radical in the core and chemically scavenges ROS. This study aimed to determine the potential neuroprotective role of RNPs on Abeta-induced cytotoxicity in human neuroblastoma SH-SY5Y cells.
  
  
  METHODS
  SH-SY5Y cells were preincubated with 0.1-1 mM RNP for 24 h and then incubated with 20 microM Abeta1-42, for 48 h. In every group, cell viability, apoptotic rate, ROS levels including superoxide anion radicals and hydroxyl radicals, ROS production including lipid peroxidation, protein oxidation and DNA oxidation were measured.
  
  
  RESULTS
  SH-SY5Y cells preincubated with 0.1-2 mM RNP for 24 h were protected from Abeta-induced damage. SH-SY5Y cells preincubated with more than 2 mM RNPfor 24 h showed cytotoxicity. From the quantitative analyses, it was observed that RNPs reduced intracellular oxidative stress. RNP treatment significantly reduced the amount of oxidized lipids, proteins and DNA. It also reduced DNA fragmentations, which caused lower apoptosis levels.
  
  
  CONCLUSIONS
  RNPs are promising intracellular ROS scavengers.
authors: Department of Materials Science, Master's School of Medical Sciences, Satellite Laboratory of International Center for Materials Nanoarchitectonics, University of Tsukuba, Tennoudai I-I-I, Tsukuba, Ibaraki 305-8573, Japan.
authors: Pennapa
authors: P
authors: Chonpathompikunlert
authors: Toru
authors: T
authors: Yoshitomi
authors: Junkyu
authors: J
authors: Han
authors: Kazuko
authors: K
authors: Toh
authors: Hiroko
authors: H
authors: Isoda
authors: Yukio
authors: Y
authors: Nagasaki
mesh_terms: D016229:Amyloid beta-Peptides / Q000633:toxicity*; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D005609:Free Radicals; D006801:Humans; D015227:Lipid Peroxidation / Q000187:drug effects; D053758:Nanoparticles / Q000008:administration & dosage*; D009447:Neuroblastoma / Q000378:metabolism / Q000473:pathology; D009589:Nitrogen Oxides / Q000008:administration & dosage*; D018384:Oxidative Stress; D010446:Peptide Fragments / Q000633:toxicity*; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D005609:Free Radicals; D009589:Nitrogen Oxides; D010446:Peptide Fragments; D017382:Reactive Oxygen Species; C075222:amyloid beta-protein (1-42); C039900:nitroxyl