Effect of gold nanoparticles on glutathione depletion-induced hydrogen peroxide generation and apoptosis in HL7702 cells

► The mechanism for GSH depletion induced by gold nanoparticles in human liver cells (HL7702). ► Cytosolic and mitochondrial GSH depletion in HL7702 cells following 8 nm gold nanoparticles treatment. ► H 2O 2 generation increased significantly following the depletion of mitochondrial GSH. ► The sequence of mitochondrial signaling events in 8 nm gold nanoparticles-induced apoptosis. 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 8 nm AuNPs at 50 nM, there was an early decline in cytosolic GSH, which initiated mitochondrial transmembrane potential (ΔΨm) depolarization and apoptosis. Mitochondrial GSH depletion was observed at approximately 48 h, after which mitochondrial hydrogen peroxide (H 2O 2) production increased significantly and apoptosis was further exacerbated. Bax translocation, cytochrome c release and downstream caspase 3 were first detected at 24 h, notably after 48 h, corresponding with increasing H 2O 2 level. These data suggest that HL7702 cells are depleted of intracellular GSH as a result that 8 nm 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 2O 2 production following mitochondrial GSH depletion represents a crucial event, which commits HL7702 cells to apoptosis through mitochondrial pathway.