| LIGHT sensitizes IFN-gamma-mediated apoptosis of HT-29 human carcinoma cells through both death receptor and mitochondria pathways. | |
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MedLine Citation:
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PMID: 15115612 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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LIGHT [homologous to lymphotoxins, shows inducible expression, and competes with herpes simplex virus glycoprotein D for herpes virus entry mediator (HVEM/TR2)] is a new member of TNF superfamily. The HT-29 colon cancer cell line is the most sensitive to LIGHT-induced, IFNg-mediated apoptosis among the cell lines we have examined so far. Besides downregulation of Bcl-XL, upregulation of Bak, and activation of both PARP [poly (ADP-ribose) polymerase] and DFF45 (DNA fragmentation factor), LIGHT-induced, IFNg-mediated apoptosis of HT-29 cells involves extensive caspase activation. Caspase-8 and caspase-9 activation, as shown by their cleavages appeared as early as 24 h after treatment, whereas caspase-3 and caspase-7 activation, as shown by their cleavages occurred after 72 h of LIGHT treatment. Caspase-3 inhibitor Z-DEVD-FMK (benzyloxycarbonyl-Asp-Glu-Val-Asp-fluoromethylketone) and a broad range caspase inhibitor Z-VAD-FMK (benzyloxycarbonyl-Val-Ala-Asp fluoromethylketone) were able to block LIGHT-induced, IFNg-mediated apoptosis of HT-29 cells. The activity of caspase-3, which is one of the major executioner caspases, was found to be inhibited by both Z-DEVD-MFK and Z-VAD-FMK. These results suggest that LIGHT-induced, IFNg-mediated apoptosis of HT-29 cells is caspase-dependent, and LIGHT signaling is mediated through both death receptor and mitochondria pathways. |
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Authors:
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Man Chao Zhang; Hong Peng Liu; Lisa L Demchik; Yi Fan Zhai; Da Jun Yang |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Cell research Volume: 14 ISSN: 1001-0602 ISO Abbreviation: Cell Res. Publication Date: 2004 Apr |
Date Detail:
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Created Date: 2004-04-29 Completed Date: 2004-12-20 Revised Date: 2008-11-21 |
Medline Journal Info:
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Nlm Unique ID: 9425763 Medline TA: Cell Res Country: China |
Other Details:
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Languages: eng Pagination: 117-24 Citation Subset: IM |
Affiliation:
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Division of Hematology/Oncology, Department of Internal Medicine, the University of Michigan, Ann Arbor, MI 48109-0934, USA. manchaoz@umich.edu |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Amino Acid Chloromethyl Ketones
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pharmacology Apoptosis / drug effects, physiology* Caspases / antagonists & inhibitors, metabolism Cysteine Proteinase Inhibitors / pharmacology Enzyme Activation / drug effects HT29 Cells Humans Interferon-gamma / metabolism*, pharmacology Membrane Proteins / metabolism*, pharmacology Mitochondria / metabolism* Oligopeptides / pharmacology Proto-Oncogene Proteins c-bcl-2 / metabolism Receptors, Tumor Necrosis Factor / metabolism* Signal Transduction* / drug effects Tumor Necrosis Factor Ligand Superfamily Member 14 Tumor Necrosis Factor-alpha / metabolism*, pharmacology bcl-2 Homologous Antagonist-Killer Protein bcl-X Protein |
| Chemical | |
Reg. No./Substance:
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0/Amino Acid Chloromethyl Ketones; 0/BAK1 protein, human; 0/BCL2L1 protein, human; 0/Cysteine Proteinase Inhibitors; 0/Membrane Proteins; 0/Oligopeptides; 0/Proto-Oncogene Proteins c-bcl-2; 0/Receptors, Tumor Necrosis Factor; 0/TNFSF14 protein, human; 0/Tumor Necrosis Factor Ligand Superfamily Member 14; 0/Tumor Necrosis Factor-alpha; 0/bcl-2 Homologous Antagonist-Killer Protein; 0/bcl-X Protein; 0/benzoylcarbonyl-aspartyl-glutamyl-valyl-aspartyl-fluoromethyl ketone; 0/benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone; 82115-62-6/Interferon-gamma; EC 3.4.22.-/Caspases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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