| Antimycin A-induced cell death depends on AIF translocation through NO production and PARP activation and is not involved in ROS generation, cytochrome c release and caspase-3 activation in HL-60 cells. | |
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MedLine Citation:
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PMID: 19229286 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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A respiratory inhibitor, antimycin A (AA), induced an apoptotic-like cell death characterized by nuclear and DNA fragmentation in human leukemia HL-60 cells. This cell death was significantly restricted by a nitric oxide synthase (NOS) inhibitor, N(G)-monomethyl-L-arginine (L-NMMA), and a poly(ADP-ribose) polymerase (PARP) inhibitor, 5-aminoisoquinoline (AIQ). Indeed, NO production and PARP overactivation were detected in the cells treated with AA. On the one hand, L-NMMA partly eliminated NO production and on the other, AIQ and L-NMMA also restricted PARP activation. Excessive signals related to PARP overactivation induce the translocation of an apoptosis-inducing factor (AIF) from the mitochondria to the nuclei, resulting in DNA fragmentation. In AA-treated cells, the nuclear translocation of AIF occurred. This translocation was restricted by pretreatment with AIQ and L-NMMA. Although pretreatment with ascorbic acid eliminated the reactive oxygen species (ROS) generation induced by the blockade of complex III by AA, the pretreatment did not protect the cells from AA-induced cell death. Furthermore, cytochrome c release or caspase-3 activation was not observed in the cells treated with AA. These results suggest that AA-induced cell death does not depend on respiratory inhibition and the succeeding cascades, but on NO production, PARP overactivation and AIF translocation. |
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Authors:
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Masaki Ogita; Akira Ogita; Yoshinosuke Usuki; Ken-ichi Fujita; Toshio Tanaka |
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Publication Detail:
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Type: Journal Article Date: 2009-02-20 |
Journal Detail:
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Title: The Journal of antibiotics Volume: 62 ISSN: 0021-8820 ISO Abbreviation: J. Antibiot. Publication Date: 2009 Mar |
Date Detail:
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Created Date: 2009-03-27 Completed Date: 2009-10-19 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0151115 Medline TA: J Antibiot (Tokyo) Country: Japan |
Other Details:
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Languages: eng Pagination: 145-52 Citation Subset: IM |
Affiliation:
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Department of Biology and Geosciences, Graduate School of Science, Osaka City University, Sumiyoshi-ku, Osaka, Japan. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Antibiotics, Antineoplastic
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pharmacology* Antimycin A / pharmacology* Apoptosis Inducing Factor / metabolism* Calpain / metabolism Caspase 3 / metabolism* Cell Death / drug effects Cell Nucleus / drug effects, ultrastructure Cytochromes c / metabolism* Cytosol / drug effects, metabolism DNA Fragmentation / drug effects Enzyme Activation / drug effects Fluorescent Dyes HL-60 Cells Humans Membrane Potentials / drug effects NAD / metabolism Nitric Oxide / biosynthesis* Poly(ADP-ribose) Polymerases / metabolism* Protein Transport Reactive Oxygen Species / metabolism* |
| Chemical | |
Reg. No./Substance:
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0/Antibiotics, Antineoplastic; 0/Apoptosis Inducing Factor; 0/Fluorescent Dyes; 0/Reactive Oxygen Species; 10102-43-9/Nitric Oxide; 53-84-9/NAD; 642-15-9/Antimycin A; 9007-43-6/Cytochromes c; EC 2.4.2.30/Poly(ADP-ribose) Polymerases; EC 3.4.22.-/Calpain; EC 3.4.22.-/Caspase 3 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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