Document Detail


Baculovirus P35 inhibits NO-induced apoptosis in activated macrophages by inhibiting cytochrome c release.
MedLine Citation:
PMID:  15173317     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The baculovirus protein P35 inhibits apoptosis in a diverse range of animals such as insects, nematodes and mammals. Evidence suggests that P35 can inhibit members of caspase family proteases that are key mediators of mammalian apoptosis. We demonstrate that p35 inhibits activation-induced nitric oxide (NO)-mediated apoptosis in the RAW 264.7 mouse macrophages. Parent or vector-transfected RAW 264.7 cells underwent apoptosis when treated with a combination of cisplatin and interferon-gamma (IFN-gamma) or LPS and IFN-gamma in a NO-dependent manner. By contrast, RAW 264.7 cells stably expressing P35 did not undergo apoptosis when treated with a combination of cisplatin and IFN-gamma or LPS and IFN-gamma. Activation of parent, vector- or p35-transfected cells with cisplatin and IFN-gamma or LPS and IFN-gamma caused equivalent levels of inducible nitric oxide synthase (iNOS) expression and produced equal amounts of nitrite, which ruled out attenuated iNOS activity during P35-mediated protection. Rather, expression of P35 inhibited translocation of mitochondrial cytochrome c into cytosol, mitochondrial depolarization, activation of caspase-9 and caspase-3, and cleavage of poly (ADP-ribose) polymerase (PARP). These findings indicate that P35 inhibits NO-induced apoptotic cell death of activated macrophages by inhibiting mitochondrial cytochrome c release, which suggests that P35 has targets upstream of the caspase cascade in apoptosis.
Authors:
Priya Ranjan; Punya Shrivastava; Sukh Mahendra Singh; Ajit Sodhi; Nicholas H Heintz
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Publication Detail:
Type:  Journal Article     Date:  2004-06-01
Journal Detail:
Title:  Journal of cell science     Volume:  117     ISSN:  0021-9533     ISO Abbreviation:  J. Cell. Sci.     Publication Date:  2004 Jun 
Date Detail:
Created Date:  2004-06-15     Completed Date:  2005-12-07     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  0052457     Medline TA:  J Cell Sci     Country:  England    
Other Details:
Languages:  eng     Pagination:  3031-9     Citation Subset:  IM    
Affiliation:
Department of Pathology and Vermont Cancer Center, University of Vermont, Burlington, VT 05405, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Apoptosis*
Baculoviridae
Caspase 3
Caspase 9
Caspases / metabolism
Cells, Cultured
Cisplatin / pharmacology
Cytochromes c / antagonists & inhibitors,  metabolism*
Enzyme Activation
Interferon-gamma / pharmacology
Lipopolysaccharides / pharmacology
Macrophages / cytology,  metabolism*
Mice
Mitochondria / metabolism
Nitric Oxide / physiology*
Poly(ADP-ribose) Polymerases / metabolism
Protein Transport
Viral Proteins / genetics,  metabolism*
Chemical
Reg. No./Substance:
0/Lipopolysaccharides; 0/Viral Proteins; 0/p35 protein, Baculovirus; 10102-43-9/Nitric Oxide; 15663-27-1/Cisplatin; 82115-62-6/Interferon-gamma; 9007-43-6/Cytochromes c; EC 2.4.2.30/Poly(ADP-ribose) Polymerases; EC 3.4.22.-/Casp3 protein, mouse; EC 3.4.22.-/Casp9 protein, mouse; EC 3.4.22.-/Caspase 3; EC 3.4.22.-/Caspase 9; EC 3.4.22.-/Caspases

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