title: Disruption of redox homeostasis and induction of apoptosis by suppression of glutathione synthetase expression in a mammalian cell line.
abstract: The stable HepG2 transfectants anti-sensing expression of the glutathione synthetase (GS) gene exhibited delayed cell growth and increased reactive oxygen species (ROS) level. After the treatment with hydrogen peroxide, the intracellular ROS level was much higher in the stable transfectants than in the vector control cells. However, the GSH levels decreased more significantly in the stable transfectants than in the vector control cells, in the presence of hydrogen peroxide. Hydrogen peroxide-induced apoptosis of the stable transfectants was notably higher than that of the vector control cells. The GS anti-sense RNAs rendered the HepG2 cells more sensitive to growth arrest caused by glucose deprivation. They also sensitized the HepG2 cells to cadmium chloride (Cd) and nitric oxide (NO)-generating sodium nitroprusside (SNP). In brief, the results confirm that GS plays an important role in the defense of the human hepatoma cells against oxidative stress by reducing apoptosis and maintaining redox homeostasis.
authors.affiliation: Department of Biochemistry, Kangwon National University, Chuncheon, Korea.
authors.forename: Su-Jung
authors.initials: SJ
authors.lastname: Kim
authors.forename: Hyun-Joo
authors.initials: HJ
authors.lastname: Jung
authors.forename: Chang-Jin
authors.initials: CJ
authors.lastname: Lim
mesh_terms: D017209:Apoptosis; D053148:Caspase 3 / Q000378:metabolism; D005721:Glutamate-Cysteine Ligase / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism*; D005981:Glutathione Synthase / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D056945:Hep G2 Cells; D006706:Homeostasis / Q000187:drug effects; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects; D016372:RNA, Antisense / Q000235:genetics; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D016372:RNA, Antisense; D017382:Reactive Oxygen Species; D009569:Nitric Oxide; D006861:Hydrogen Peroxide; D053148:Caspase 3; D005721:Glutamate-Cysteine Ligase; D005981:Glutathione Synthase; D005978:Glutathione