Document Detail


Presentation of nitric oxide regulates monocyte survival through effects on caspase-9 and caspase-3 activation.
MedLine Citation:
PMID:  12566444     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
In the absence of survival factors, blood monocytes undergo spontaneous apoptosis, which involves the activation of caspase-3. Although nitric oxide can block caspase-3 activation and promote cell survival, it can also induce apoptosis. We hypothesized that nitrosothiols that promote protein S-nitrosylation would reduce caspase-3 activation and cell survival, whereas nitric oxide donors (such as 1-propamine 3-(2-hydroxy-2-nitroso-1-propylhydrazine (PAPA) NONOate and diethylamine (DEA) NONOate) that do not target thiol residues would not. Using human monocytes as a model, we observed that nitrosothiol donors S-nitrosoglutathione and S-nitroso-N-acetylpenicillamine suppressed caspase-9 and caspase-3 activity and DNA fragmentation. In contrast, PAPA or DEA NONOate did not promote monocyte survival events and appeared to inhibit monocyte survival induced by macrophage colony-stimulating factor. The caspase-3-selective inhibitor DEVD-fluoromethyl ketone reversed DNA fragmentation events, and the caspase-9 inhibitor LEHD-fluoromethyl ketone reversed caspase-3 activity in monocytes treated with PAPA or DEA NONOate in the presence of macrophage colony-stimulating factor. These results were not caused by differences in glutathione levels or the kinetics of nitric oxide release. Moreover, S-nitrosoglutathione and S-nitroso-N-acetylpenicillamine directly blocked the activity of recombinant caspase-3, which was reversed by the reducing agent dithiothreitol, whereas PAPA or DEA NONOate did not block the enzymatic activity of caspase-3. These data support the hypothesis that nitrosylation of protein thiol residues by nitric oxide is critical for promoting the survival of human monocytes.
Authors:
Mandy M Zeigler; Andrea I Doseff; Michelle F Galloway; Judy M Opalek; Philip T Nowicki; Jay L Zweier; Chandan K Sen; Clay B Marsh
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Publication Detail:
Type:  In Vitro; Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.     Date:  2003-02-03
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  278     ISSN:  0021-9258     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  2003 Apr 
Date Detail:
Created Date:  2003-04-07     Completed Date:  2003-07-03     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  12894-902     Citation Subset:  IM    
Affiliation:
Dorothy M. Davis Heart and Lung Research Institute, the Department of Internal Medicine, Ohio State University, Columbus, Ohio 43210-1252, USA.
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MeSH Terms
Descriptor/Qualifier:
Caspase 3
Caspase 9
Caspases / blood*
Cell Survival / drug effects*
DNA Fragmentation / drug effects
Enzyme Activation
Glutathione / blood
Humans
Hydrazines / pharmacology
Kinetics
Monocytes / cytology*,  drug effects,  enzymology
Nitric Oxide / pharmacology*
Nitric Oxide Donors / pharmacology*
Nitrogen Oxides
S-Nitrosoglutathione
Grant Support
ID/Acronym/Agency:
HL63800/HL/NHLBI NIH HHS; HL66108/HL/NHLBI NIH HHS; HL67176/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Hydrazines; 0/Nitric Oxide Donors; 0/Nitrogen Oxides; 0/PAPA NONOate; 10102-43-9/Nitric Oxide; 57564-91-7/S-Nitrosoglutathione; 70-18-8/Glutathione; 86831-65-4/1,1-diethyl-2-hydroxy-2-nitrosohydrazine; EC 3.4.22.-/CASP3 protein, human; EC 3.4.22.-/CASP9 protein, human; EC 3.4.22.-/Caspase 3; EC 3.4.22.-/Caspase 9; EC 3.4.22.-/Caspases

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