| Spontaneous human monocyte apoptosis utilizes a caspase-3-dependent pathway that is blocked by endotoxin and is independent of caspase-1. | |
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MedLine Citation:
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PMID: 10438906 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Apoptosis is an important mechanism for regulating the numbers of monocytes and macrophages. Caspases (cysteine-aspartate-specific proteases) are key molecules in apoptosis and require proteolytic removal of prodomains for activity. Caspase-1 and caspase-3 have both been connected to apoptosis in other model systems. The present study attempted to delineate what role these caspases play in spontaneous monocyte apoptosis. In serum-free conditions, monocytes showed a commitment to apoptosis as early as 4 h in culture, as evidenced by caspase-3-like activity. Apoptosis, as defined by oligonucleosomal DNA fragmentation, was prevented by a generalized caspase inhibitor, z-VAD-FMK, and the more specific caspase inhibitor, z-DEVD-FMK. The caspase activity was specifically attributable to caspase-3 by the identification of cleavage of procaspase-3 to active forms by immunoblots and by cleavage of the fluorogenic substrate DEVD-AFC. In contrast, a caspase-1 family inhibitor, YVAD-CMK, did not protect monocytes from apoptosis, and the fluorogenic substrate YVAD-AFC failed to show an increase in activity in apoptotic monocytes. When cultured with LPS (1 microgram/ml), monocyte apoptosis was prevented, as was the activation of caspase-3. Unexpectedly, LPS did not change baseline caspase-1 activity. These findings link spontaneous monocyte apoptosis to the proteolytic activation of caspase-3. |
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Authors:
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R J Fahy; A I Doseff; M D Wewers |
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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: Journal of immunology (Baltimore, Md. : 1950) Volume: 163 ISSN: 0022-1767 ISO Abbreviation: J. Immunol. Publication Date: 1999 Aug |
Date Detail:
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Created Date: 1999-09-09 Completed Date: 1999-09-09 Revised Date: 2007-11-14 |
Medline Journal Info:
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Nlm Unique ID: 2985117R Medline TA: J Immunol Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 1755-62 Citation Subset: AIM; IM |
Affiliation:
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Department of Internal Medicine, Division of Pulmonary and Critical Care, The Heart and Lung Institute, Ohio State University, Columbus, OH 43210, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Apoptosis
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immunology* Caspase 1 / physiology* Caspase 3 Caspases / antagonists & inhibitors, blood, physiology* Cell Survival / immunology Enzyme Activation / immunology Humans Interleukin-1 / metabolism Lipopolysaccharides / pharmacology* Monocytes / cytology*, enzymology*, immunology Protein Precursors / metabolism Signal Transduction / immunology |
| Grant Support | |
ID/Acronym/Agency:
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HL40871/HL/NHLBI NIH HHS; HL53229/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Interleukin-1; 0/Lipopolysaccharides; 0/Protein Precursors; EC 3.4.22.-/CASP3 protein, human; EC 3.4.22.-/Caspase 3; EC 3.4.22.-/Caspases; EC 3.4.22.36/Caspase 1 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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