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.

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