Activation of the intrinsic mitochondrial apoptotic pathway in swine influenza virus-mediated cell death.
- Author:
Young Ki CHOI
1
;
Tae Kyung KIM
;
Chul Joong KIM
;
Joong Seob LEE
;
Se Young OH
;
Han Soo JOO
;
Douglas N FOSTER
;
Ki Chang HONG
;
Seungkwon YOU
;
Hyunggee KIM
Author Information
1. College of Medicine and Medical Research Institute, Chungbuk National University, Cheongju 361-711, Korea.
- Publication Type:Original Article ; Comparative Study ; Research Support, Non-U.S. Gov't
- Keywords:
apoptosis;
cytochrome c;
influenza virus;
mitochondria;
proto-oncogene proteins c-Bcl-2;
proto-oncogene proteins c-jun
- MeSH:
Animals;
Annexin A5/metabolism;
*Apoptosis;
Blotting, Western;
Cell Fractionation;
Cell Line;
Comparative Study;
Cytochrome c Group/metabolism;
Cytosol/chemistry;
DNA Fragmentation;
Enzyme Activation;
Gene Expression Regulation, Viral;
Hela Cells;
Humans;
Influenza A virus/*physiology;
Kinetics;
Mitochondria/metabolism/*physiology;
Precipitin Tests;
Proto-Oncogene Proteins c-bcl-2/genetics/metabolism;
Research Support, Non-U.S. Gov't;
Swine;
bcl-2-Associated X Protein/genetics/metabolism
- From:Experimental & Molecular Medicine
2006;38(1):11-17
- CountryRepublic of Korea
- Language:English
-
Abstract:
The mitochondrial pathway of swine influenza virus (SIV)-induced apoptosis was investigated using porcine kidney (PK-15) cells, swine testicle (ST) cells, and HeLa cervical carcinoma cells which are known not to support viral replication. As judged by cell morphology, annexin V staining, and DNA fragmentation, PK-15 and ST cells infected with three different subtypes of SIV (H1N1, H3N2, and H1N2) were obviously killed by apoptosis, not necrosis. SIV infection in PK-15 and HeLa cells was shown to decrease the cellular levels of Bcl-2 protein compared to that of mock-infected control cells at 24 h post-infection, whereas expression levels of Bax protein increased in the PK-15 cells, but did not increase in HeLa cells by SIV infection. Cytochrome c upregulation was also observed in cytosolic fractions of the PK-15 and HeLa cells infected with SIV. Apoptosome (a multi-protein complex consisting of cytochrome c, Apaf-1, caspase-9, and ATP) formation was confirmed by immunoprecipitation using cytochrome c antibody. Furthermore, SIV infection increased the cellular levels of TAJ, an activator of the JNK-stressing pathway, and the c-Jun protein in the PK-15 and HeLa cells. Taken together, these results suggest that the mitochondrial pathway should be implicated in the apoptosis of PK-15 cells induced by SIV infection.
