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CoCl2 induces apoptosis through the mitochondria- and death receptor-mediated pathway in the mouse embryonic stem cells

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Abstract

Embryonic hypoxia/ischemia is a major cause of a poor fetal outcome and future neonatal and adult handicaps. However, biochemical cellular events in mouse embryonic stem (mES) cells during hypoxia remains unclear. This study investigated the underlying mechanism of apoptosis in mES cells under CoCl2-induced hypoxic/ischemic conditions. CoCl2 enhanced the expression of hypoxia-inducible factor-1α (HIF-1α) and the accumulation of reactive oxygen species in mES cells. The CoCl2-treated mES cells showed a decrease in cell viability as well as typical apoptotic changes, cell shrinkage, chromatin condensation, and nuclear fragmentation and an extended G2/M phase of the cell cycle. CoCl2 augmented the release of cytochrome c into the cytosol from the mitochondria with a concomitant loss of the mitochondrial transmembrane potential (ΔΨm) and upregulated the voltage-dependent anion channel. In addition, CoCl2-induced caspase-3, -8, and -9 activation and upregulation of p53 level, whereas downregulated Bcl-2 and Bcl-xL, a member of the anti-apoptotic Bcl-2 family in mES cells. Furthermore, CoCl2 led to the upregulation of Fas and Fas-ligand, which are the death receptor assemblies, as well as the cleavage of Bid in mES cells. These results suggest that CoCl2 induces apoptosis through both mitochondria- and death receptor-mediated pathways that are regulated by the Bcl-2 family in mES cells.

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Acknowledgments

This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (2009-0075373 and 2010-0006901) and was supported by the National Research Foundation of Korea (NRF) Grants funded by the Korea government (MEST) (2011-0030761 and 2011-0029663).

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Authors and Affiliations

  1. Research Center for Biomineralization Disorder, Dental Science Research Institute, School of Dentistry, Chonnam National University, Gwangju, 500-757, South Korea

    Jin-Ha Lee, Seong-Ho Choi, Min-Woo Baek, Mi-Hwa Kim, Heong-Jun Kim, Sun-Hun Kim, Hong-Ju Park, Won-Jae Kim & Ji-Yeon Jung

  2. School of Biological Sciences and Technology, Chonnam National University, Gwangju, 500-757, South Korea

    Sang-Jin Oh

  3. Central Research Institute, Pharmacology Department, Shinpoong Pharmaceutical company, Gyeonggi, 425-100, South Korea

    Heong-Jun Kim

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  1. Jin-Ha Lee
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Correspondence to Won-Jae Kim or Ji-Yeon Jung.

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Lee, JH., Choi, SH., Baek, MW. et al. CoCl2 induces apoptosis through the mitochondria- and death receptor-mediated pathway in the mouse embryonic stem cells. Mol Cell Biochem 379, 133–140 (2013). https://doi.org/10.1007/s11010-013-1635-5

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  • DOI: https://doi.org/10.1007/s11010-013-1635-5

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