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Control of Oxidative Stress and Generation of Induced Pluripotent Stem Cell-like Cells by Jun Dimerization Protein 2
Division of Hematology-Oncology, Department of Pediatrics, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan
Department of Pediatrics, Faculty of Medicine, School of Medicine, Kaohsiung Medical University, 807 Kaohsiung 807, Taiwan
Department of Gastroenterology, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan
School of Dentistry, College of Dentistry, Kaohsiung Medical University, Kaohsiung 807, Taiwan
Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, 807 Kaohsiung 807, Taiwan
Department of Surgery, Cancer Center, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan
Department of Pathology, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan
RIKEN BioResource Center, Tsukuba, Ibaraki 305-0074, Japan
Saito Laboratory of Cell Technology, Yaita, Tochigi 329-1571, Japan
Graduate School of Pharmaceutical Science, Chiba University, Chiba 260-8675, Japan
Department of Biochemistry & Molecular Biology, UMDNJ-New Jersey Medical School, Newark, NJ 07101, USA
* Authors to whom correspondence should be addressed.
Received: 3 June 2013; in revised form: 12 July 2013 / Accepted: 18 July 2013 / Published: 26 July 2013
Abstract: We report here that the Jun dimerization protein 2 (JDP2) plays a critical role as a cofactor for the transcription factors nuclear factor-erythroid 2-related factor 2 (Nrf2) and MafK in the regulation of the antioxidants and production of reactive oxygen species (ROS). JDP2 associates with Nrf2 and MafK (Nrf2-MafK) to increase the transcription of antioxidant response element-dependent genes. Oxidative-stress-inducing reagent led to an increase in the intracellular accumulation of ROS and cell proliferation in Jdp2 knock-out mouse embryonic fibroblasts. In Jdp2-Cre mice mated with reporter mice, the expression of JDP2 was restricted to granule cells in the brain cerebellum. The induced pluripotent stem cells (iPSC)-like cells were generated from DAOY medulloblastoma cell by introduction of JDP2, and the defined factor OCT4. iPSC-like cells expressed stem cell-like characteristics including alkaline phosphatase activity and some stem cell markers. However, such iPSC-like cells also proliferated rapidly, became neoplastic, and potentiated cell malignancy at a later stage in SCID mice. This study suggests that medulloblastoma cells can be reprogrammed successfully by JDP2 and OCT4 to become iPSC-like cells. These cells will be helpful for studying the generation of cancer stem cells and ROS homeostasis.
Keywords: anti oxidation; iPSC-like cells; Jun dimerization protein 2; medulloblastoma; ROS; oxidative stress
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Chiou, S.-S.; Wang, S.S.-W.; Wu, D.-C.; Lin, Y.-C.; Kao, L.-P.; Kuo, K.-K.; Wu, C.-C.; Chai, C.-Y.; Lin, C.-L.S.; Lee, C.-Y.; Liao, Y.-M.; Wuputra, K.; Yang, Y.-H.; Wang, S.-W.; Ku, C.-C.; Nakamura, Y.; Saito, S.; Hasegawa, H.; Yamaguchi, N.; Miyoshi, H.; Lin, C.-S.; Eckner, R.; Yokoyama, K.K. Control of Oxidative Stress and Generation of Induced Pluripotent Stem Cell-like Cells by Jun Dimerization Protein 2. Cancers 2013, 5, 959-984.
Chiou S-S, Wang SS-W, Wu D-C, Lin Y-C, Kao L-P, Kuo K-K, Wu C-C, Chai C-Y, Lin C-LS, Lee C-Y, Liao Y-M, Wuputra K, Yang Y-H, Wang S-W, Ku C-C, Nakamura Y, Saito S, Hasegawa H, Yamaguchi N, Miyoshi H, Lin C-S, Eckner R, Yokoyama KK. Control of Oxidative Stress and Generation of Induced Pluripotent Stem Cell-like Cells by Jun Dimerization Protein 2. Cancers. 2013; 5(3):959-984.
Chiou, Shyh-Shin; Wang, Sophie S.-W.; Wu, Deng-Chyang; Lin, Ying-Chu; Kao, Li-Pin; Kuo, Kung-Kai; Wu, Chun-Chieh; Chai, Chee-Yin; Lin, Cheng-Lung S.; Lee, Cheng-Yi; Liao, Yu-Mei; Wuputra, Kenly; Yang, Ya-Han; Wang, Shin-Wei; Ku, Chia-Chen; Nakamura, Yukio; Saito, Shigeo; Hasegawa, Hitomi; Yamaguchi, Naoto; Miyoshi, Hiroyuki; Lin, Chang-Sheng; Eckner, Richard; Yokoyama, Kazunari K. 2013. "Control of Oxidative Stress and Generation of Induced Pluripotent Stem Cell-like Cells by Jun Dimerization Protein 2." Cancers 5, no. 3: 959-984.