Early activation of the mitochondrial apoptotic pathway in Vesicular Stomatitis virus-infected cells.
Vesicular Stomatitis Virus (VSV) has been shown to induce apoptosis in a caspase-dependent manner, but the precise apoptotic pathway remains unknown. We found that caspases 9 and 3, but not caspase 8, were activated during VSV-induced apoptosis in infected Vero cells. Since caspase 9 is related to the mitochondrial apoptotic pathway, we analyzed some mitochondrial events such as changes in the mitochondrial transmembrane potential (Deltapsim) and mitochondrial release of apoptogenic proteins such as cytochrome c and the apoptosis inducing factor (AIF). We found that VSV infection triggers the dissipation of the Deltapsim and the release of both cytochrome c and AIF from the mitochondrial intermembrane space very early in the VSV infection. These results indicate that the trigger of apoptosis in VSV-infected cells occurs through the early activation of the mitochondrial apoptotic pathway. On the other hand, intracellular levels of the anti-apoptotic proteins, such as Bcl-2 and Bcl-xL, and the pro-apoptotic protein Bax, were assessed during viral infection. These analyses showed that as viral infection proceeded, the cellular level of Bcl-xL decreased, while the levels of Bax and Bcl-2 remained unaffected. The significance of the Bcl-xL modulation is also discussed.
Gadaleta
Patricia
P
Department of Biological Chemistry, School of Sciences, University of Buenos Aires, Ciudad Universitaria, Pabellón II, Piso 4, Buenos Aires 1428, Argentina. Pat@qb.fcen.uba.ar
Perfetti
Ximena
X
Mersich
Susana
S
Coulombié
Félix
F
D000818:Animals; D017209:Apoptosis; D051033:Apoptosis Inducing Factor; D053148:Caspase 3; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases / Q000378:metabolism; D002522:Chlorocebus aethiops; D045304:Cytochromes c / Q000378:metabolism; D004789:Enzyme Activation; D005420:Flavoproteins / Q000032:analysis; D008564:Membrane Potentials; D008565:Membrane Proteins / Q000032:analysis; D008928:Mitochondria / Q000378:metabolism / Q000502:physiology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D014709:Vero Cells; D014721:Vesicular stomatitis Indiana virus / Q000472:pathogenicity*; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein
D051033:Apoptosis Inducing Factor; D005420:Flavoproteins; D008565:Membrane Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein; D045304:Cytochromes c; D053148:Caspase 3; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases