Top

Research Article

Split Viewer

Mol. Cells 2010; 30(4): 311-318

Published online October 31, 2010

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

© The Korean Society for Molecular and Cellular Biology

Overexpression of Ornithine Decarboxylase Suppresses Thapsigargin-Induced Apoptosis

Wei-Chung Hsieh1,2, Pei-Chen Hsu2,3, Ya-Fan Liao4, Shu-Ting Young3, Zeng-Wei Wang5, Chih-Li Lin1, Gregory J. Tsay5,6, Huei Lee7,8, Hui-Chih Hung3,*, and Guang-Yaw Liu5,*

1Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan, R.O.C., 2Department of Internal Medicine, Da-Chien General Hospital, Miao-Li, Taiwan, R.O.C., 3Department of Life Sciences, National Chung-Hsing University, Taichung, Taiwan, R.O.C., 4Institute of Biochemical Sciences and Technology, Chaoyang University of Technology, Wufong, Taiwan, R.O.C., 5Institute of Microbiology and Immunology, Chung-Shan Medical University, and Division of Allergy, Immunology, and Rheumatology, Chung-Shan Medical University Hospital, Taichung, Taiwan, R.O.C., 6Department of Medicine, Chung Shan Medical University, Taichung, Taiwan, R.O.C., 7Institute of Medical and Molecular Toxicology, Chung Shan Medical University, Taichung, Taiwan, R.O.C., 8Lung Cancer Research Center, Chung Shan Medical University, Taichung, Taiwan, R.O.C.

Correspondence to : *Correspondence: liugy@csmu.edu.tw(GL)/hchung@dragon.nchu.edu.tw (HH)

Received: March 2, 2010; Revised: July 16, 2010; Accepted: July 20, 2010

Abstract

Ornithine decarboxylase (ODC), the key enzyme of polya-mine biosynthesis, has paradoxical roles in apoptosis. Our published papers show overexpression of ODC pre-vents the apoptosis induced by many cytotoxic drugs. Thapsigargin (TG) is an inhibitor of the sarcoplasmic/en-doplasmic reticulum (ER) Ca2+ ATPase (SERCA) pumps and causes ER stress-induced apoptosis. We used ODC overexpressing cell lines to examine whether overexpres-sion 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 downstream caspase activation were blocked. That is, overexpression of ODC inhibits the mitochondria-medi-ated 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.

Keywords endoplasmic reticulum (ER), mitochondrial membrane potential, ornithine decarboxylase (ODC), thapsigargin (TG)

Article

Research Article

Mol. Cells 2010; 30(4): 311-318

Published online October 31, 2010 https://doi.org/10.1007/s10059-010-0120-1

Copyright © The Korean Society for Molecular and Cellular Biology.

Overexpression of Ornithine Decarboxylase Suppresses Thapsigargin-Induced Apoptosis

Wei-Chung Hsieh1,2, Pei-Chen Hsu2,3, Ya-Fan Liao4, Shu-Ting Young3, Zeng-Wei Wang5, Chih-Li Lin1, Gregory J. Tsay5,6, Huei Lee7,8, Hui-Chih Hung3,*, and Guang-Yaw Liu5,*

1Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan, R.O.C., 2Department of Internal Medicine, Da-Chien General Hospital, Miao-Li, Taiwan, R.O.C., 3Department of Life Sciences, National Chung-Hsing University, Taichung, Taiwan, R.O.C., 4Institute of Biochemical Sciences and Technology, Chaoyang University of Technology, Wufong, Taiwan, R.O.C., 5Institute of Microbiology and Immunology, Chung-Shan Medical University, and Division of Allergy, Immunology, and Rheumatology, Chung-Shan Medical University Hospital, Taichung, Taiwan, R.O.C., 6Department of Medicine, Chung Shan Medical University, Taichung, Taiwan, R.O.C., 7Institute of Medical and Molecular Toxicology, Chung Shan Medical University, Taichung, Taiwan, R.O.C., 8Lung Cancer Research Center, Chung Shan Medical University, Taichung, Taiwan, R.O.C.

Correspondence to:*Correspondence: liugy@csmu.edu.tw(GL)/hchung@dragon.nchu.edu.tw (HH)

Received: March 2, 2010; Revised: July 16, 2010; Accepted: July 20, 2010

Abstract

Ornithine decarboxylase (ODC), the key enzyme of polya-mine biosynthesis, has paradoxical roles in apoptosis. Our published papers show overexpression of ODC pre-vents the apoptosis induced by many cytotoxic drugs. Thapsigargin (TG) is an inhibitor of the sarcoplasmic/en-doplasmic reticulum (ER) Ca2+ ATPase (SERCA) pumps and causes ER stress-induced apoptosis. We used ODC overexpressing cell lines to examine whether overexpres-sion 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 downstream caspase activation were blocked. That is, overexpression of ODC inhibits the mitochondria-medi-ated 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.

Keywords: endoplasmic reticulum (ER), mitochondrial membrane potential, ornithine decarboxylase (ODC), thapsigargin (TG)

Mol. Cells
Sep 30, 2022 Vol.45 No.9, pp. 603~672
COVER PICTURE
The Target of Rapamycin Complex (TORC) is a central regulatory hub in eukaryotes, which is well conserved in diverse plant species, including tomato (Solanum lycopersicum). Inhibition of TORC genes (SlTOR, SlLST8, and SlRAPTOR) by VIGS (virus-induced gene silencing) results in early fruit ripening in tomato. The red/ orange tomatoes are early-ripened TORC-silenced fruits, while the green tomato is a control fruit. Top, left, control fruit (TRV2-myc); top, right, TRV2-SlLST8; bottom, left, TRV2-SlTOR; bottom, right, TRV2-SlRAPTOR(Choi et al., pp. 660-672).

Share this article on

  • line
  • mail

Molecules and Cells

eISSN 0219-1032
qr-code Download