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Research Papers:

Quercetin induced ROS production triggers mitochondrial cell death of human embryonic stem cells

So-Yeon Kim, Ho-Chang Jeong, Soon-Ki Hong, Mi-Ok Lee, Seung-Ju Cho, Hyuk-Jin Cha _

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Abstract

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

Correspondence to:

Hyuk-Jin Cha, email: hjcha@sogang.ac.kr

Seung-Ju Cho, email: sjcho122108@gmail.com

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

ABSTRACT

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.

Author Information

So-Yeon Kim

Ho-Chang Jeong

Soon-Ki Hong

Mi-Ok Lee

Seung-Ju Cho

Hyuk-Jin Cha
Primary Contact  _


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