Involvement of VDAC1 and Bcl-2 family of proteins in VacA-induced cytochrome c release and apoptosis of gastric epithelial carcinoma cells.
OBJECTIVE
It is known that the vacuolating cytotoxin (VacA) could induce apoptosis. However, the mechanism remained to be elucidated. The aim of this study is to investigate the role of Bcl family of proteins (Bcl-2 and Bax) and the mitochondrial voltage-dependent anion channel (VDAC) in VacA-induced apoptosis of AGS cells.


METHODS
Plasmid pGBKT7-VacA p58 was constructed and transfected into the AGS cells. RT-PCR and Western blotting were used to determine the expressions of cytochrome c, caspase-3, Bax, Bcl-2 and VDAC1 mRNA and proteins.


RESULTS
VacA p58 can induce cytochrome c release and activate caspase-3 in AGS cells. It up-regulated the expressions of Bax and VDAC1 mRNA and proteins, and decreased the expression of Bcl-2 in AGS cells.


CONCLUSIONS
VacA p58 induces apoptosis in AGS cells. This apoptotic process is associated with the up-regulation of Bax/VDAC1 and downregulation of Bcl-2. These findings suggest that the release of cytochrome c by VacA p58 is mainly through VDAC-dependent and Bcl-2 family-dependent pathways.
Lan
Chun Hui
CH
Department of Gastroenterology, Daping Hospital, Third Military Medical College, Chongqing, China. tiandaochouqin99@hotmail.com
Sheng
Jian Qiu
JQ
Fang
Dian Chun
DC
Meng
Qing Zhuang
QZ
Fan
Li Lin
LL
Huang
Zeng Rong
ZR
D017209:Apoptosis / Q000235:genetics / Q000502:physiology*; D001426:Bacterial Proteins / Q000235:genetics / Q000502:physiology*; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D045304:Cytochromes c / Q000378:metabolism*; D015536:Down-Regulation; D005838:Genotype; D006801:Humans; D009375:Neoplasms, Glandular and Epithelial / Q000382:microbiology* / Q000503:physiopathology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D013274:Stomach Neoplasms / Q000382:microbiology* / Q000503:physiopathology; D015854:Up-Regulation; D050995:Voltage-Dependent Anion Channel 1 / Q000378:metabolism*
D001426:Bacterial Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; C494762:VDAC1 protein, human; C074689:VacA protein, Helicobacter pylori; D045304:Cytochromes c; D050995:Voltage-Dependent Anion Channel 1; D053148:Caspase 3