Quercetin induced ROS production triggers mitochondrial cell death of human embryonic stem cells
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So-Yeon Kim1, Ho-Chang Jeong1, Soon-Ki Hong1, Mi-Ok Lee2, Seung-Ju Cho1 and Hyuk-Jin Cha1
1College of Natural Sciences, Department of Life Sciences, Sogang University, Seoul 121–742, Korea
2Stem Cell Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon 305–806, Korea
Hyuk-Jin Cha, email: [email protected]
Seung-Ju Cho, email: [email protected]
Keywords: quercetin, human embryonic stem cells (hESCs), reactive oxygen species (ROS), p53, cyclophilin D
Received: March 30, 2016 Accepted: July 19, 2016 Published: August 05, 2016
Small molecules to selectively induce cell death of undifferentiated human pluripotent stem cells (hPSCs) have been developed with the aim of lowering the risk of teratoma formation during hPSC-based cell therapy. In this context, we have reported that Quercetin (QC) induces cell death selectively in hESCs via p53 mitochondrial localization. However, the detailed molecular mechanism by which hESCs undergo selective cell death induced by QC remains unclear.
Herein, we demonstrate that mitochondrial reactive oxygen species (ROS), strongly induced by QC in human embryonic stem cells (hESCs) but not in human dermal fibroblasts (hDFs), were responsible for QC-mediated hESC’s cell death. Increased p53 protein stability and subsequent mitochondrial localization by QC treatment triggered mitochondrial cell death only in hESCs. Of interest, peptidylprolyl isomerase D [PPID, also called cyclophilin D (CypD)], which functions in mitochondrial permeability transition and mitochondrial cell death, was highly expressed in hESCs. Inhibition of CypD by cyclosporine A (CsA) clearly inhibited the QC-mediated loss of mitochondrial membrane potential and mitochondrial cell death. These results suggest that p53 and CypD in the mitochondria are critical for the QC-mediated induction of cell death in hESCs.
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