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614121 
Journal Article 
Endoplasmic Reticulum Stress and Unfolded Protein Response in Atm-Deficient Thymocytes and Thymic Lymphoma Cells Are Attributed to Oxidative Stress 
Mingshan, Y; Jianjun, S; Person, MD; Xianghong, K; Lynn, WS; Atlas, D; Wong, PKY 
2008 
1 
Neoplasia
ISSN: 1522-8002
EISSN: 1476-5586 
10 
2 
160-167 
Both oxidative stress and endoplasmic reticulum (ER) stress have been implicated in carcinogenesis. It is well documented that cells deficient in the ataxia--telangiectasia mutated (ATM) gene undergo oxidative stress, which is critically involved in thymic lymphomagenesis in Atm-/- mice. Here we demonstrate that undifferentiated Atm-/- thymocytes show signs of ER stress and of the unfolded protein response (UPR). Using two-dimensional (2-D) gel electrophoresis and mass spectrometry (MS) analysis, we identified 22 differentially expressed proteins, including the ER stress marker glucose-regulated protein 78 (GRP78), in Atm-/- thymocytes and in Atm-/- thymic lymphoma cells relative to Atm+/+ thymocytes. The phosphorylated a subunit of eukaryotic translation initiation factor 2 (p-eIF2α), a UPR marker, was also increased in Atm-/- thymocytes. Cells of the ATL-1 line, which were derived from an Atm-/- mouse thymic lymphoma, were more sensitive to the ER stress inducer tunicamycin than were Atm+/+ thymic leukemia ASL-1 cells. Notably, treatment with hydrogen peroxide duplicated the effects of ATM deficiency in cultured thymocytes, and treatment with the novel cell-permeable thiol antioxidant N-acetylcysteine amide (AD4) reduced elevated p-eIF2α levels in thymocytes of Atm-/- mice. Thus, we propose that ER stress and the UPR are secondary to oxidative stress in Atm-/- thymocytes. [ABSTRACT FROM AUTHOR] Copyright of Neoplasia is the property of Neoplasia Press and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts) 
OXIDATIVE stress; ENDOPLASMIC reticulum; PROTEINS -- Denaturation; CARCINOGENESIS; ATAXIA telangiectasia; MICE as laboratory animals; HYDROGEN peroxide; THIOLS