| Overexpression of ornithine decarboxylase suppresses thapsigargin-induced apoptosis. | |
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MedLine Citation:
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PMID: 20814750 Owner: NLM Status: In-Process |
Abstract/OtherAbstract:
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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) Ca(2+) 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 procaspase-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:
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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 |
Publication Detail:
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Type: Journal Article Date: 2010-08-31 |
Journal Detail:
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Title: Molecules and cells Volume: 30 ISSN: 0219-1032 ISO Abbreviation: Mol. Cells Publication Date: 2010 Oct |
Date Detail:
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Created Date: 2010-11-05 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9610936 Medline TA: Mol Cells Country: United States |
Other Details:
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Languages: eng Pagination: 311-8 Citation Subset: IM |
Affiliation:
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Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan, ROC. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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