To investigate the function of the oxidative stress in the endoplasmic reticulum (ER) -related cell death of glioma, the human glioma cells were treated with hydrogen peroxide, TNF, and thapsigargin to raise intracellular levels of hydroxyl radical and ER stress, respectively. Hydrogen peroxide and thapsigargin increased cytosolic Ca2+, induced the activation of caspase 3, and caused apoptosis in a dose-dependent manner. In contrast, TNF affect neither cell viability nor the increase of cytosolic Ca2+. Both hydrogen peroxide and thapsigargin increased the expressions of ER-associated molecules including p-PERK, IRE1-α, p-eIF, ATF-1, p-CREB and Ero1-α in human glioma cells, whereas TNF did not increase the expressions of them. Hydrogen peroxide and thapsigargin increased IRE1-α nuclease activity generating transcriptionally active form of XBP-1 and induced IRE1-α-TRAF2 complex formation which initiates JNK activation and increase of expressions of p-JNK1 and p-JNK2. On the other hand, TNF-α did not increase p-JNK1and p-JNK 2 levels. IRE1-α induction coincided with those of p-JNK1, p-JNK and induced formation of IRE1-α-TRAF2 in hydrogen peroxide- and thapsigargin- treated cells. Therefore, we conclude that the increase of expression of IRE1-α is necessary for activating TRAF2-JNK pathway and causing oxidative stress- induced cell death of glioma.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2084. doi:10.1158/1538-7445.AM2011-2084
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.