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Overexpression of ornithine decarboxylase suppresses thapsigargin-induced apoptosis

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Molecules and Cells

Abstract

Ornithine decarboxylase (ODC), the key enzyme of polyamine biosynthesis, has paradoxical roles in apoptosis. Our published papers show overexpression of ODC prevents the apoptosis induced by many cytotoxic drugs. Thapsigargin (TG) is an inhibitor of the sarcoplasmic/endoplasmic reticulum (ER) Ca2+ ATPase (SERCA) pumps and causes ER stress-induced apoptosis. We used ODC overexpressing cell lines to examine whether overexpression of ODC inhibits TG-induced apoptosis. Our results indicated overexpression of ODC attenuated TG-induced apoptosis. Overexpression of ODC blocked procaspse-4 cleavage and phosphorylation of protein kinase-like ER-resident kinase (PERK), triggered by TG. It also attenuated the increase in CAAT/enhancer binding protein homologous protein (CHOP). Cells with overexpressed ODC had greater Bcl-2 expression. Overexpression of ODC preserved the expression of Bcl-2, inhibited the increase in Bak and stabilized mitochondrial membrane potential without the influences of TG. Cytochrome c release and down-stream caspase activation were blocked. That is, overexpression of ODC inhibits the mitochondria-mediated apoptotic pathway, induced by TG. Finally, overexpression of ODC maintains the protein and mRNA expression of SERCA. In conclusion, overexpression of ODC suppresses TG-induced apoptosis by blocking caspase-4 activation and PERK phosphorylation, attenuating CHOP expression and inhibiting the mitochondria-mediated apoptotic pathway.

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Authors and Affiliations

  1. Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan, R.O.C.

    Wei-Chung Hsieh & Chih-Li Lin

  2. Department of Internal Medicine, Da-Chien General Hospital, Miao-Li, Taiwan, R.O.C.

    Wei-Chung Hsieh & Pei-Chen Hsu

  3. Department of Life Sciences, National Chung-Hsing University, Taichung, Taiwan, R.O.C.

    Pei-Chen Hsu, Shu-Ting Young & Hui-Chih Hung

  4. Institute of Biochemical Sciences and Technology, Chaoyang University of Technology, Wufong, Taiwan, R.O.C.

    Ya-Fan Liao

  5. Institute of Microbiology and Immunology, Chung-Shan Medical University, Taichung, Taiwan, R.O.C.

    Zeng-Wei Wang, Gregory J. Tsay & Guang-Yaw Liu

  6. Division of Allergy, Immunology, and Rheumatology, Chung-Shan Medical University Hospital, Taichung, Taiwan, R.O.C.

    Zeng-Wei Wang, Gregory J. Tsay & Guang-Yaw Liu

  7. Department of Medicine, Chung Shan Medical University, Taichung, Taiwan, R.O.C.

    Gregory J. Tsay

  8. Institute of Medical and Molecular Toxicology, Chung Shan Medical University, Taichung, Taiwan, R.O.C.

    Huei Lee

  9. Lung Cancer Research Center, Chung Shan Medical University, Taichung, Taiwan, R.O.C.

    Huei Lee

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  1. Wei-Chung Hsieh
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  2. Pei-Chen Hsu
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  9. Hui-Chih Hung
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  10. Guang-Yaw Liu
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Correspondence to Hui-Chih Hung or Guang-Yaw Liu.

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Hsieh, WC., Hsu, PC., Liao, YF. et al. Overexpression of ornithine decarboxylase suppresses thapsigargin-induced apoptosis. Mol Cells 30, 311–318 (2010). https://doi.org/10.1007/s10059-010-0120-1

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  • DOI: https://doi.org/10.1007/s10059-010-0120-1

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