GRP78 levels have been reported to increase in cells following cytotoxic-induced ER stress, where it contributes to cell survival. According to reports that metals are implicated in the etiology or pathogenesis of Alzheimer’s disease, some metals such as lead induce the expression of GRP78, which is often associated with oxidative stress, and Pb impairs GRP78 function following binding. Moreover, it has been reported that GRP78 may play a role in the modulation of the sensitivity of cells to stress after oxidative injury. Increases in the mRNA expression of GRP78 are Tubeimoside-I observed in retinal pigment epithelial cells exposed to oxidative stress. Experiments using cultured neurons reveal that GRP78 may protect cells Benzoylpaeoniflorin against oxidative stress via actions involving mainly the maintenance of calcium homeostasis. Meanwhile, it was reported that GRP78 expression did not increase when cells were exposed to H2O2, which suggested that H2O2 exposure may not induce the ER stress pathway. In our study, an increase in GRP78 expression in C6 cells was not observed after treatment with H2O2, however, the viability of cells decreased. Considering previous reports, our results suggest that GRP78 itself could play an important role in protecting cells against H2O2 injury regardless of whether the pathways that mediate GRP78 expression respond to their extracellular stimuli. H2O2 causes cytotoxicity via the formation of more potent oxidants including OH?, which causes lipid peroxidation of the cell membrane. Lipid peroxidation disrupts the normal structure of cellular and subcellular membranes. In addition, the process produces byproducts such as 4-hydroxynonenal or acrolein, both of which bind to proteins and damage their structure and function. The present results show that GRP78 overexpressing cells suppress lipid peroxidation and may contribute to cell survival following H2O2 treatment. These data suggest that GRP78 can promote the expression of some antioxidants and may contribute to the protection of cells against H2O2 injury. While a number of antioxidants are involved in the detoxification of H2O2, GSH is the primary defense against H2O2. GSH inhibits lipid peroxidation initiation by scavenging OH? or other ROS. Moreover, GSH also serves as a co-factor for GSH peroxidases that remove H2O2. It was reported that GSH was useful for curtailment of lipid peroxidation damage in acute spinal cord injury. The ratio of GSH reduces when an increase in ROS induces ER stress. In our results, when cells were exposed to H2O2, GSH expression in GRP78 overexpressing cells was high when compared with non-GRP78 overexpressing cells. These results suggest that the increase of GRP78 by gene transfection may contribute to the increase in GSH or inhibit GSH consumption, thus leading to cell survival. We observed the influence of GRP78 on NQO1 in this study. NQO1 catalyzes the electron reduction of quinone and quinoid compounds to hydroquinones, thus limiting the formation of semiquinone radicals, and the subsequent generation of ROS. According to reports regarding the role of NQO1, H2O2dependent formation of reactive oxygen intermediates was shown to be reduced following treatment with neuroprotective agents that induce NQO1 expression. In our results, NQO1 expression levels in GRP78 overexpressing cells was higher than in non-GRP78 overexpressing cells. This phenomenon continued following H2O2 exposure. These findings indicate that GRP78 may be advantageous to the expression of NQO1. NQO1 has the ability to use both NADPH and NADH equally efficiently, thus NQO1 may contribute to the regulation of the redox balance by modulating reduced/oxidized pyridine nucleotide ratios. NADPH is required to reduce oxidized glutathione to GSH.