Expression of dengue ApoptoM sequence results in disruption of mitochondrial potential and caspase activation.
Apoptotic cell death has been involved as a cytopathologic mechanism in response to dengue (DEN) virus infection. Little information exists about how DEN virus replication triggers apoptosis in infected cells. We reported that a nine-residue sequence of the DEN M protein referred to as ApoptoM has proapoptotic properties in transformed and tumor cells of various origins. The aim of the present study was to investigate whether ApoptoM-induced apoptosis is associated to mitochondrial dysfunction and requires caspase activation. Intracellular expression of ApoptoM provokes the disruption of the mitochondrial transmembrane potential without subsequent generation of reactive oxygen species. We showed that ApoptoM-induced apoptosis involves the activation of a caspase-like protease pathway. Caspase-3 like activity was detected in ApoptoM-expressing cells. However, there was no role for caspase-9 in ApoptoM-mediated cell death. Our data suggest that a particular mitochondrion-dependent apoptotic pathway may be involved in induction of apoptosis by ApoptoM.
Unité des Interactions Moléculaires Flavivirus-Hôtes, Institut Pasteur, 25, rue du Dr-Roux, 75015 Paris, France.
Adeline
A
Catteau
Gaël
G
Roué
Victor J
VJ
Yuste
Santos A
SA
Susin
Philippe
P
Desprès
D000590:Amino Acid Chloromethyl Ketones / Q000494:pharmacology; D000595:Amino Acid Sequence; D017209:Apoptosis / Q000502:physiology; D053148:Caspase 3; D053453:Caspase 9; D061945:Caspase Inhibitors; D020169:Caspases / Q000378:metabolism*; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D003716:Dengue Virus / Q000472:pathogenicity; D004789:Enzyme Activation; D049452:Green Fluorescent Proteins; D006367:HeLa Cells / Q000473:pathology; D006801:Humans; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D008564:Membrane Potentials / Q000502:physiology*; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000494:pharmacology; D011065:Poly(ADP-ribose) Polymerases / Q000187:drug effects / Q000378:metabolism; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D019311:Staurosporine / Q000494:pharmacology; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism*
D000590:Amino Acid Chloromethyl Ketones; D061945:Caspase Inhibitors; D015853:Cysteine Proteinase Inhibitors; D008164:Luminescent Proteins; D009842:Oligopeptides; D011994:Recombinant Proteins; D014764:Viral Proteins; C403754:benzyloxycarbonyl-leucyl-glutamyl-histidyl-aspartic acid fluoromethyl ketone; C096713:benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone; C084187:prM protein, Dengue virus type 3; D049452:Green Fluorescent Proteins; D011065:Poly(ADP-ribose) Polymerases; C505407:CASP3 protein, human; C506433:CASP9 protein, human; D053148:Caspase 3; D053453:Caspase 9; D020169:Caspases; D019311:Staurosporine