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Pyrrolidine dithiocarbamate-induced activation of ERK and increased expression of c-Fos in mouse embryonic stem cells

  • Kim, Young-Eun (Department of Biochemistry, College of Natural Sciences, Chungbuk National University) ;
  • Park, Jeong-A (Department of Biochemistry, College of Natural Sciences, Chungbuk National University) ;
  • Nam, Ki-Hoan (Bio-Evaluation Center, Korea Research Institute of Bioscience and Biotechnology) ;
  • Kwon, Hyung-Joo (Center for Medical Science Research, College of Medicine, Hallym University) ;
  • Lee, Young-Hee (Department of Biochemistry, College of Natural Sciences, Chungbuk National University)
  • Published : 2009.03.31

Abstract

Pyrrolidine dithiocarbamate (PDTC) is a stable anti-oxidant or pro-oxidant, depending on the situation, and it is widely used to inhibit the activation of NF-${\kappa}B$. We recently reported that PDTC activates the MIP-2 gene in a NF-${\kappa}B$-independent and c-Jun-dependent manner in macrophage cells. In this work, we found that PDTC activates signal transduction pathways in mouse ES cells. Among the three different mitogen-activated protein kinase (MAPK) pathways, including the extracellular-signal-regulated kinase (ERK), p38 MAP kinase, and stress-activated protein kinase (SAPK)/Jun N-terminal kinase (JNK) pathways, only the ERK pathway was significantly activated in mouse ES cells after stimulation with PDTC. Additionally, we observed a synergistic activation of ERK and induction of c-Fos after stimulation with PDTC in the presence of mouse embryonic fibroblast (MEF) conditioned medium. In contrast, another NF-${\kappa}B$ inhibitor, BMS-345541, did not activate the MAP kinase pathways or induce expression of c-Fos. These results suggest that changes in the presence of the NF-${\kappa}B$ inhibitor PDTC should be carefully considered when it used with mouse ES cells.

Keywords

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