Caspase-8 and Apaf-1-independent caspase-9 activation in Sendai virus-infected cells.
Apoptotic cell death is of central importance in the pathogenesis of viral infections. Activation of a cascade of cysteine proteases, i.e. caspases, plays a key role in the effector phase of virus-induced apoptosis. However, little is known about pathways leading to the activation of initiator caspases in virus-infected host cells. Recently, we have shown that Sendai virus (SeV) infection triggers apoptotic cell death by activation of the effector caspase-3 and initiator caspase-8. We now investigated mechanisms leading to the activation of another initiator caspase, caspase-9. Unexpectedly we found that caspase-9 cleavage is not dependent on the presence of active caspases-3 or -8. Furthermore, the presence of caspase-9 in mouse embryonic fibroblast (MEF) cells was a prerequisite for Sendai virus-induced apoptotic cell death. Caspase-9 activation occurred without the release of cytochrome c from mitochondria and was not dependent on the presence of Apaf-1 or reactive oxygen intermediates. Our results therefore suggest an alternative mechanism for caspase-9 activation in virally infected cells beside the well characterized pathways via death receptors or mitochondrial cytochrome c release.
Bitzer
Michael
M
Department of Internal Medicine I, University Clinic Tübingen, D-72076 Tübingen, Germany. michael.bitzer@uni-tuebingen.de
Armeanu
Sorin
S
Prinz
Florian
F
Ungerechts
Guy
G
Wybranietz
Wolfgang
W
Spiegel
Martin
M
Bernlöhr
Christian
C
Cecconi
Francesco
F
Gregor
Michael
M
Neubert
Wolfgang J
WJ
Schulze-Osthoff
Klaus
K
Lauer
Ulrich M
UM
D000818:Animals; D053477:Apoptotic Protease-Activating Factor 1; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases / Q000378:metabolism*; D004789:Enzyme Activation; D006801:Humans; D006868:Hydrolysis; D051379:Mice; D011506:Proteins / Q000378:metabolism*; D017382:Reactive Oxygen Species; D029082:Sendai virus / Q000502:physiology*; D014407:Tumor Cells, Cultured
C506592:APAF1 protein, human; C506593:Apaf1 protein, mouse; D053477:Apoptotic Protease-Activating Factor 1; D011506:Proteins; D017382:Reactive Oxygen Species; C505530:CASP8 protein, human; C506433:CASP9 protein, human; C505526:Casp8 protein, mouse; C506434:Casp9 protein, mouse; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases