| Temporal ordering of caspase activation and substrate cleavage during antigen receptor-triggered apoptosis in Ramos-Burkitt lymphoma B cells. | |
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MedLine Citation:
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PMID: 12851674 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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We demonstrate here that selective activation of endogenous members of the caspase family and cleavage of substrates responsible for the maintenance of nuclear functional and structural integrity are major effectors of antigen receptor (AgR)- and ionomycin-triggered apoptosis in Ramos-Burkitt lymphoma (Ramos-BL) B cells. Ramos-BL B cells express significant proenzyme levels of caspase-2, -3, -7 and -8, low levels of caspase-6 and are caspase-1-negative. However, while anti-IgM and ionomycin trigger for significant activation of caspase-3, -7 and -8 at 12-16 h and at 4 h post-stimulation respectively, both anti-IgM and ionomycin fail to activate caspase-2 indicating that AgR- and ionomycin-triggered Ramos-BL B cell apoptosis is mediated by the selective activation of, at least, caspase-3, -7 and -8. Anti-IgM triggers for cleavage of the resident nuclear proteins poly(ADP-ribose) polymerase (PARP) at 8 h, lamins B1 and B2 from 12 to 16 h; likewise, ionomycin triggers for degradation of PARP at 2 h, lamins B1 and B2 at 4 h. Signal transduction through CD40 rescues Ramos-BL B cells from AgR- and ionomycin-triggered apoptosis at a very early stage of the apoptotic process by inhibiting both the early cleavage of PARP as well as the activation of caspase-3, -7 and -8 and cleavage of lamin B1; CD40-mediated rescue occurs upstream of CD40-induced expression of Bcl-2 and increased expression of Bcl-xL. In such cellular populations subject to regulation through apoptosis, dysregulation of the apoptotic mechanisms can have devastating consequences by contributing to the pathogenesis of malignancy as well as to lymphoproliferative and autoantibody disorders. An understanding of the role played by caspases in the execution of apoptosis may provide insight into the pathogenesis of these disease states and thereby provide targets for novel therapeutic strategy. |
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Authors:
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Sungkwan An; In-Chul Park; Chang Hun Rhee; Seok-Il Hong; Kirstine Knox |
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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: International journal of oncology Volume: 23 ISSN: 1019-6439 ISO Abbreviation: Int. J. Oncol. Publication Date: 2003 Aug |
Date Detail:
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Created Date: 2003-07-09 Completed Date: 2004-03-04 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 9306042 Medline TA: Int J Oncol Country: Greece |
Other Details:
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Languages: eng Pagination: 257-68 Citation Subset: IM |
Affiliation:
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Department of Biochemistry, University of Oxford, UK. genomicslab@hanmail.net |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Antigens, CD40
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immunology,
metabolism* Apoptosis / drug effects*, physiology B-Lymphocytes / cytology*, immunology, metabolism Burkitt Lymphoma / metabolism*, pathology Caspase 1 Caspases / metabolism* Cell Cycle / drug effects Child Enzyme Activation Enzyme Inhibitors / pharmacology Enzyme Precursors / metabolism HL-60 Cells Humans Immunoglobulin M / pharmacology Ionomycin / pharmacology Ionophores / pharmacology Jurkat Cells Lamin Type B / metabolism Male Poly(ADP-ribose) Polymerases / metabolism Proto-Oncogene Proteins c-bcl-2 / metabolism Receptors, Antigen, B-Cell / metabolism* bcl-X Protein |
| Chemical | |
Reg. No./Substance:
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0/Antigens, CD40; 0/BCL2L1 protein, human; 0/Enzyme Inhibitors; 0/Enzyme Precursors; 0/Immunoglobulin M; 0/Ionophores; 0/Lamin Type B; 0/Proto-Oncogene Proteins c-bcl-2; 0/Receptors, Antigen, B-Cell; 0/bcl-X Protein; 0/lamin B1; 0/lamin B2; 56092-81-0/Ionomycin; EC 2.4.2.30/Poly(ADP-ribose) Polymerases; 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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