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Control of Oxidative Stress and Generation of Induced Pluripotent Stem Cell-like Cells by Jun Dimerization Protein 2.

Chiou SS, Wang SS, Wu DC, Lin YC, Kao LP, Kuo KK, Wu CC, Chai CY, Lin CL, Lee CY, Liao YM, Wuputra K, Yang YH, Wang SW, Ku CC, Nakamura Y, Saito S, Hasegawa H, Yamaguchi N, Miyoshi H, Lin CS, Eckner R, Yokoyama KK - Cancers (Basel) (2013)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Division of Hematology-Oncology, Department of Pediatrics, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan. chiouss@kmu.edu.tw.

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.

No MeSH data available.


Related in: MedlinePlus

Gene expression of 2F- and 4F-iPSC-like cells. Quantitative real time PCR assay for expression of OCT4, SOX2, KLF4, and NANOG in human DAOY, 2F-and 4F-iPSC-like cells. Individual PCR reactions were normalized against internal control (GAPDH) and plotted relative to the expression level in DAOY. The sequences of the primers were shown in Table 3.
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cancers-05-00959-f006: Gene expression of 2F- and 4F-iPSC-like cells. Quantitative real time PCR assay for expression of OCT4, SOX2, KLF4, and NANOG in human DAOY, 2F-and 4F-iPSC-like cells. Individual PCR reactions were normalized against internal control (GAPDH) and plotted relative to the expression level in DAOY. The sequences of the primers were shown in Table 3.

Mentions: Transcriptions of OCT4, SOX2, c-MYC, and KLF4 were also detected and quantitated their expressions in the iPSC-like cells (Figure 6). In particular, the expression of SOX2 was significantly higher than other stemness genes in 2F- and 4F-iPSC-like cells. In 4F-iPSC-like cells, the oncogenes such as C-MYC and KLF4 were not expressed higher, instead the stemness genes such as SOX2 and NANOG expressed at significant levels (5.3–9.1-fold, respectively). By contrast, 2F-iPSC-like cells only showed higher expression of SOX2. In both iPSC-like cells, expression of oncogenic c-MYC was repressed significantly.


Control of Oxidative Stress and Generation of Induced Pluripotent Stem Cell-like Cells by Jun Dimerization Protein 2.

Chiou SS, Wang SS, Wu DC, Lin YC, Kao LP, Kuo KK, Wu CC, Chai CY, Lin CL, Lee CY, Liao YM, Wuputra K, Yang YH, Wang SW, Ku CC, Nakamura Y, Saito S, Hasegawa H, Yamaguchi N, Miyoshi H, Lin CS, Eckner R, Yokoyama KK - Cancers (Basel) (2013)

Gene expression of 2F- and 4F-iPSC-like cells. Quantitative real time PCR assay for expression of OCT4, SOX2, KLF4, and NANOG in human DAOY, 2F-and 4F-iPSC-like cells. Individual PCR reactions were normalized against internal control (GAPDH) and plotted relative to the expression level in DAOY. The sequences of the primers were shown in Table 3.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3795374&req=5

cancers-05-00959-f006: Gene expression of 2F- and 4F-iPSC-like cells. Quantitative real time PCR assay for expression of OCT4, SOX2, KLF4, and NANOG in human DAOY, 2F-and 4F-iPSC-like cells. Individual PCR reactions were normalized against internal control (GAPDH) and plotted relative to the expression level in DAOY. The sequences of the primers were shown in Table 3.
Mentions: Transcriptions of OCT4, SOX2, c-MYC, and KLF4 were also detected and quantitated their expressions in the iPSC-like cells (Figure 6). In particular, the expression of SOX2 was significantly higher than other stemness genes in 2F- and 4F-iPSC-like cells. In 4F-iPSC-like cells, the oncogenes such as C-MYC and KLF4 were not expressed higher, instead the stemness genes such as SOX2 and NANOG expressed at significant levels (5.3–9.1-fold, respectively). By contrast, 2F-iPSC-like cells only showed higher expression of SOX2. In both iPSC-like cells, expression of oncogenic c-MYC was repressed significantly.

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Division of Hematology-Oncology, Department of Pediatrics, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan. chiouss@kmu.edu.tw.

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.

No MeSH data available.


Related in: MedlinePlus