| Critical role for death-receptor mediated apoptotic signaling in viral myocarditis. | |
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MedLine Citation:
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PMID: 21055654 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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BACKGROUND: Apoptosis of cardiac myocytes plays a key role in the pathogenesis of many cardiac diseases, including viral myocarditis. The apoptotic signaling pathways that are activated during viral myocarditis and the role that these pathways play in disease pathogenesis have not been clearly delineated. METHODS AND RESULTS: We investigated the role of apoptotic signaling pathways after virus infection of primary cardiac myocytes. The death receptor-associated initiator caspase, caspase 8, and the effector caspase, caspase 3, were significantly activated after infection of primary cardiac myocytes with myocarditic, but not non-myocarditic, reovirus strains. Furthermore, reovirus-induced cardiac myocyte apoptosis was significantly inhibited by soluble death receptors. In contrast, the mitochondrial membrane potential remained unaltered and caspase 9, the initiator caspase associated with mitochondrial apoptotic signaling, was only weakly activated in cardiac myocytes after infection with myocarditic reovirus strains. Inhibition of mitochondrial apoptotic signaling had no effect on reovirus-induced cardiac myocyte apoptosis. In accordance with our in vitro data, caspase 8, but not caspase 9, was significantly activated in the hearts of reovirus-infected mice. CONCLUSIONS: Death receptor, but not mitochondrial, apoptotic signaling plays a key role in apoptosis after infection of cardiac myocytes with myocarditic reovirus strains. |
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Authors:
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Roberta L DeBiasi; Bridget A Robinson; J Smith Leser; R Dale Brown; Carlin S Long; Penny Clarke |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S. |
Journal Detail:
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Title: Journal of cardiac failure Volume: 16 ISSN: 1532-8414 ISO Abbreviation: J. Card. Fail. Publication Date: 2010 Nov |
Date Detail:
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Created Date: 2010-11-08 Completed Date: 2011-03-24 Revised Date: 2011-11-01 |
Medline Journal Info:
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Nlm Unique ID: 9442138 Medline TA: J Card Fail Country: United States |
Other Details:
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Languages: eng Pagination: 901-10 Citation Subset: IM |
Copyright Information:
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Copyright © 2010 Elsevier Inc. All rights reserved. |
Affiliation:
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Department of Pediatrics, Children's National Medical Center and George Washington University School of Medicine, Washington, DC 20010, USA. rdebiasi@cnmc.org |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Apoptosis* Caspase 3 / metabolism Caspase 8 / metabolism Mice Myocarditis / pathology, virology* Myocytes, Cardiac / pathology* Rats Receptors, Death Domain / metabolism* Reoviridae Infections / metabolism Signal Transduction |
| Grant Support | |
ID/Acronym/Agency:
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AI052261 (K08)/AI/NIAID NIH HHS; HL79160/HL/NHLBI NIH HHS; NS050138 (RO1)/NS/NINDS NIH HHS; NS051403 (RO1)/NS/NINDS NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Receptors, Death Domain; EC 3.4.22.-/Caspase 3; EC 3.4.22.-/Caspase 8 |
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