Overexpression of ornithine decarboxylase suppresses thapsigargin-induced apoptosis

Wei Chung Hsieh, Pei Chen Hsu, Ya Fan Liao, Shu Ting Young, Zeng Wei Wang, Chih Li Lin, Gregory J. Tsay, Huei Lee, Hui Chih Hung, Guang Yaw Liu

Research output: Contribution to journalArticle

9 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)311-318
Number of pages8
JournalMolecules and Cells
Volume30
Issue number4
DOIs
Publication statusPublished - Oct 2010
Externally publishedYes

Keywords

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

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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  • Cite this

    Hsieh, W. C., Hsu, P. C., Liao, Y. F., Young, S. T., Wang, Z. W., Lin, C. L., Tsay, G. J., Lee, H., Hung, H. C., & Liu, G. Y. (2010). Overexpression of ornithine decarboxylase suppresses thapsigargin-induced apoptosis. Molecules and Cells, 30(4), 311-318. https://doi.org/10.1007/s10059-010-0120-1