title: Effect of gold nanoparticles on glutathione depletion-induced hydrogen peroxide generation and apoptosis in HL7702 cells.
abstract: Gold nanoparticles (AuNPs) have shown promising biological and military applications due to their unique electronic and optical properties. However, little is known about their cytotoxicity when they come into contact with a biological system. The primary objective of this study is to determine the sequence of apoptotic signaling events that occur after modulation of the cellular redox state in HL7702 cells (human liver cell line), with emphasis on the role of the interaction of AuNPs with glutathione (GSH). After incubation with 8nm AuNPs at 50nM, there was an early decline in cytosolic GSH, which initiated mitochondrial transmembrane potential (ΔΨm) depolarization and apoptosis. Mitochondrial GSH depletion was observed at approximately 48h, after which mitochondrial hydrogen peroxide (H(2)O(2)) production increased significantly and apoptosis was further exacerbated. Bax translocation, cytochrome c release and downstream caspase 3 were first detected at 24h, notably after 48h, corresponding with increasing H(2)O(2) level. These data suggest that HL7702 cells are depleted of intracellular GSH as a result that 8nm AuNPs possess strong Au-S bonding interactions with GSH. A decrease in GSH alone can act as a potent early activator of apoptotic signaling. Increased H(2)O(2) production following mitochondrial GSH depletion represents a crucial event, which commits HL7702 cells to apoptosis through mitochondrial pathway.
authors.affiliation: College of Chemistry, Chemical Engineering and Materials Science Engineering Research Center of Pesticide and Medicine Intermediate Clean Production, Ministry of Education Key Laboratory of Molecular and Nano Probes Ministry of Education, Shandong Normal University, Jinan 250014, People's Republic of China.
authors.forename: Wen
authors.initials: W
authors.lastname: Gao
authors.forename: Kehua
authors.initials: K
authors.lastname: Xu
authors.forename: Lifei
authors.initials: L
authors.lastname: Ji
authors.forename: Bo
authors.initials: B
authors.lastname: Tang
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D045304:Cytochromes c / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D005978:Glutathione / Q000172:deficiency* / Q000378:metabolism; D006046:Gold / Q000633:toxicity*; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism*; D008564:Membrane Potentials / Q000187:drug effects; D046529:Microscopy, Electron, Transmission; D008930:Mitochondria, Liver / Q000187:drug effects / Q000378:metabolism; D051336:Mitochondrial Membranes / Q000187:drug effects; D053758:Nanoparticles / Q000633:toxicity; D010316:Particle Size; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D051028:bcl-2-Associated X Protein; D006046:Gold; D045304:Cytochromes c; D006861:Hydrogen Peroxide; D053148:Caspase 3; D005978:Glutathione