| Granzyme B of cytotoxic T cells induces extramitochondrial reactive oxygen species production via caspase-dependent NADPH oxidase activation. | |
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MedLine Citation:
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PMID: 20125115 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Induction of reactive oxygen species (ROS) is a hallmark of granzyme B (gzmB)-mediated pro-apoptotic processes and target cell death. However, it is unclear to what extent the generated ROS derive from mitochondrial and/or extra-mitochondrial sources. To clarify this point, we have produced a mutant EL4 cell line, termed EL4-rho(0), which lacks mitochondrial DNA, associated with a decreased mitochondrial membrane potential and a defective ROS production through the electron transport chain of oxidative phosphorylation. When incubated with either recombinant gzmB plus streptolysin or ex vivo gzmB(+) cytotoxic T cells, EL4-rho(0) cells showed phosphatydylserine translocation, caspase 3 activation, Bak conformational change, cytochrome c release and apoptotic morphology comparable to EL4 cells. Moreover, EL4-rho(0) cells produced ROS at levels similar to EL4 under these conditions. GzmB-mediated ROS production was almost totally abolished in both cell lines by the pan-caspase inhibitor, Z-VAD-fmk. However, addition of apocynin, a specific inhibitor of nicotinamide adenine dinucleotide phosphate (NADPH) oxidases, led to a significant reduction of ROS production and cell death only in EL4-rho(0) but not EL4 cells. These data suggest that gzmB-induced cell death is accompanied by a caspase-dependent pathway of extra-mitochondrial ROS production, most probably through activation of NADPH oxidase. |
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Authors:
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Juan I Aguiló; Alberto Anel; Elena Catalán; Alvaro Sebastián; Rebeca Acín-Pérez; Javier Naval; Reinhard Wallich; Markus M Simon; Julián Pardo |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-02-02 |
Journal Detail:
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Title: Immunology and cell biology Volume: 88 ISSN: 1440-1711 ISO Abbreviation: Immunol. Cell Biol. Publication Date: 2010 Jul |
Date Detail:
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Created Date: 2010-07-02 Completed Date: 2010-09-28 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8706300 Medline TA: Immunol Cell Biol Country: England |
Other Details:
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Languages: eng Pagination: 545-54 Citation Subset: IM |
Affiliation:
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Departamento de Bioquímica y Biología Molecular y Celular, Universidad de Zaragoza, Zaragoza, Spain. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Apoptosis / immunology Caspases / immunology*, metabolism Cell Line Enzyme Activation / immunology Granzymes / immunology*, metabolism Humans Immunoblotting Mice Mice, Inbred C57BL Mitochondria / immunology, metabolism NADPH Oxidase / immunology, metabolism Reactive Oxygen Species / immunology*, metabolism Reverse Transcriptase Polymerase Chain Reaction Signal Transduction / immunology* T-Lymphocytes, Cytotoxic / immunology*, metabolism |
| Chemical | |
Reg. No./Substance:
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0/Reactive Oxygen Species; EC 1.6.3.1/NADPH Oxidase; EC 3.4.21.-/Granzymes; EC 3.4.22.-/Caspases |
| Comments/Corrections | |
Comment In:
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Immunol Cell Biol. 2010 Jul;88(5):500-1
[PMID:
20231855
]
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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