| Arsenic trioxide (As(2)O(3)) induces apoptosis through activation of Bax in hematopoietic cells. | |
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MedLine Citation:
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PMID: 15735709 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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This study explores the roles of Bax and other Bcl-2 family members play in arsenic trioxide (As(2)O(3))-induced apoptosis. We showed that As(2)O(3) treatment triggered Bax conformational change and subsequent translocation from cytosol to mitochondria to form various multimeric homo-oligomers in IM-9 cells. On the other hand, human leukemic Jurkat cells deficient in Bax showed dramatically reduced apoptosis in response to As(2)O(3). Stable overexpression of Bcl-2 in IM-9 cells (IM-9/Bcl-2) inhibited As(2)O(3)-mediated Bax activation and apoptosis, and this inhibition could be partially averted by cell-permeable Bid-Bcl-2 homology (BH)3 peptide. Meanwhile, Bax conformational change and oligomerization induced by As(2)O(3) were not inhibited by the pancaspase inhibitor z-VAD-fmk, although Bid cleavage could be completely abolished. Bax activation by As(2)O(3) seemed to require stress-induced intracellular reactive oxygen species (ROS), since the ROS scavengers (N-acetyl-L-cysteine and lipoic acid) could completely block the conformational change and translocation of Bax from cytosol to mitochondria. These data suggest that As(2)O(3) might exert the cell killing in part by inducing Bax activation through a Bcl-2-suppressible pathway in hematopoietic cells that is caspase independent and intracellular ROS regulated. |
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Authors:
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Yanhua Zheng; Hirohito Yamaguchi; Changhai Tian; Michael W Lee; Hong Tang; Hong-Gang Wang; Quan Chen |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: Oncogene Volume: 24 ISSN: 0950-9232 ISO Abbreviation: Oncogene Publication Date: 2005 May |
Date Detail:
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Created Date: 2005-05-05 Completed Date: 2005-05-31 Revised Date: 2007-11-14 |
Medline Journal Info:
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Nlm Unique ID: 8711562 Medline TA: Oncogene Country: England |
Other Details:
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Languages: eng Pagination: 3339-47 Citation Subset: IM |
Affiliation:
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The Laboratory of Apoptosis and Cancer Biology, The National Key Laboratory of Biomembrane and Membrane Biotechnology, The Institute of Zoology, Chinese Academy of Sciences, Beijing 100080, People's Republic of China. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Annexin A5
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pharmacology Antineoplastic Agents / pharmacology* Apoptosis* Arsenicals / pharmacology* Coloring Agents / pharmacology Cytosol / metabolism Dose-Response Relationship, Drug Enzyme Activation Hematopoietic Stem Cells / metabolism* Humans Jurkat Cells Mitochondria / metabolism Oxides / pharmacology* Peptides / chemistry Protein Conformation Protein Transport Proto-Oncogene Proteins c-bcl-2 / metabolism* Reactive Oxygen Species Subcellular Fractions / metabolism Time Factors bcl-2-Associated X Protein |
| Grant Support | |
ID/Acronym/Agency:
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CA82197/CA/NCI NIH HHS; CA90315/CA/NCI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Annexin A5; 0/Antineoplastic Agents; 0/Arsenicals; 0/BAX protein, human; 0/Coloring Agents; 0/Oxides; 0/Peptides; 0/Proto-Oncogene Proteins c-bcl-2; 0/Reactive Oxygen Species; 0/bcl-2-Associated X Protein; 1327-53-3/arsenic trioxide |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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