| U937 apoptotic cell death by nitric oxide: Bcl-2 downregulation and caspase activation. | |
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MedLine Citation:
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PMID: 9457054 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Upon treatment with NO-releasing compounds such as S-nitrosoglutathione or spermine NO, human myeloid leukemia U937 cells undergo apoptosis. Early NO-mediated signals comprise activation of a Z-A-DCB (benzoyloxycarbonyl-Asp-CH2OC(O)-2,6-dichlorobenzene)-sensit ive, caspase-3 like cysteine protease that cleaved poly (ADP-ribose) polymerase (PARP), U1 small nuclear ribonucleoprotein (U1 snRNP), and the fluorogenic substrate N-acetyl-Asp-Glu-Val-Asp-7-amido-4-methylcoumarin. In association with these early apoptotic alterations p21 (WAF1/Cip1) is upregulated, but NO affected cell proliferation and apoptosis at a similar dose. At later time points the classical antiapoptotic protein Bcl-2 is downregulated, indicating that decreased Bcl-2 expression is secondary and not a prerequisite for initiation of apoptosis. N-Acetylcysteine (1 mM) interfered with NO-mediated apoptotic signaling, blocking DNA fragmentation as well as PARP and U1 snRNP cleavage. In contrast Z-A-DCB suppressed DNA fragmentation and U1 snRNP cleavage, while PARP breakdown proceeded unaltered. Observing proteolytic PARP digestion without apoptotic alterations questions PARP cleavage as an apoptotic parameter. These results suggest that a Z-A-DCB-sensitive caspase that is distinct from the PARP-cleaving enzyme is activated during NO exposure. NO-mediated apoptotic signaling in U937 cells activates caspases, some of which are dispensable for propagating the death signal. |
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Authors:
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F Brockhaus; B Brüne |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Experimental cell research Volume: 238 ISSN: 0014-4827 ISO Abbreviation: Exp. Cell Res. Publication Date: 1998 Jan |
Date Detail:
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Created Date: 1998-02-23 Completed Date: 1998-02-23 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 0373226 Medline TA: Exp Cell Res Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 33-41 Citation Subset: IM |
Affiliation:
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Faculty of Medicine, Department of Medicine IV-Experimental Division, University of Erlangen-Nürnberg, Germany. |
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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drug effects* Caspase 3 Caspases* Cysteine Endopeptidases / metabolism* DNA Fragmentation DNA, Neoplasm / analysis Enzyme Activation Gene Expression Regulation, Neoplastic / drug effects Glutathione / analogs & derivatives*, pharmacology Humans Nitric Oxide / pharmacology* Nitrogen Oxides Nitroso Compounds / pharmacology* Poly(ADP-ribose) Polymerases / metabolism Proto-Oncogene Proteins c-bcl-2 / biosynthesis* Ribonucleoproteins, Small Nuclear / metabolism S-Nitrosoglutathione Spermine / analogs & derivatives*, pharmacology Tumor Cells, Cultured |
| Chemical | |
Reg. No./Substance:
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0/DNA, Neoplasm; 0/Nitrogen Oxides; 0/Nitroso Compounds; 0/Proto-Oncogene Proteins c-bcl-2; 0/Ribonucleoproteins, Small Nuclear; 10102-43-9/Nitric Oxide; 136587-13-8/spermine nitric oxide complex; 57564-91-7/S-Nitrosoglutathione; 70-18-8/Glutathione; 71-44-3/Spermine; EC 2.4.2.30/Poly(ADP-ribose) Polymerases; EC 3.4.22.-/CASP3 protein, human; EC 3.4.22.-/Caspase 3; EC 3.4.22.-/Caspases; EC 3.4.22.-/Cysteine Endopeptidases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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