RGD Reference Report - Critical role for death-receptor mediated apoptotic signaling in viral myocarditis. - Rat Genome Database

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Critical role for death-receptor mediated apoptotic signaling in viral myocarditis.

Authors: DeBiasi, Roberta L  Robinson, Bridget A  Leser, J Smith  Brown, R Dale  Long, Carlin S  Clarke, Penny 
Citation: DeBiasi RL, etal., J Card Fail. 2010 Nov;16(11):901-10. doi: 10.1016/j.cardfail.2010.05.030.
RGD ID: 13702877
Pubmed: (View Article at PubMed) PMID:21055654
DOI: Full-text: DOI:10.1016/j.cardfail.2010.05.030


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.

Annotation

Disease Annotations    
Viral Myocarditis  (IDA,ISO)

Objects Annotated

Genes (Rattus norvegicus)
Casp3  (caspase 3)
Casp8  (caspase 8)

Genes (Mus musculus)
Casp3  (caspase 3)
Casp8  (caspase 8)

Genes (Homo sapiens)
CASP3  (caspase 3)
CASP8  (caspase 8)


Additional Information