VDAC1 和 Bcl-2 家族蛋白在 VacA 诱导的胃上皮癌细胞细胞色素 c 释放和凋亡中的作用。
Involvement of VDAC1 and Bcl-2 family of proteins in VacA-induced cytochrome c release and apoptosis of gastric epithelial carcinoma cells.
机构信息
Department of Gastroenterology, Daping Hospital, Third Military Medical College, Chongqing, China.
出版信息
J Dig Dis. 2010 Feb;11(1):43-9. doi: 10.1111/j.1751-2980.2009.00412.x.
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.
CONCLUSION
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.
目的
已知空泡细胞毒素（VacA）可诱导细胞凋亡，但具体机制尚不清楚。本研究旨在探讨 Bcl 家族蛋白（Bcl-2 和 Bax）和线粒体电压依赖性阴离子通道（VDAC）在 VacA 诱导 AGS 细胞凋亡中的作用。
方法
构建质粒 pGBKT7-VacA p58 并转染 AGS 细胞。采用 RT-PCR 和 Western blot 法检测细胞色素 c、caspase-3、Bax、Bcl-2 和 VDAC1mRNA 和蛋白的表达。
结果
VacA p58 可诱导 AGS 细胞中细胞色素 c 的释放和 caspase-3 的激活。它上调 Bax 和 VDAC1mRNA 和蛋白的表达，下调 AGS 细胞中 Bcl-2 的表达。
结论
VacA p58 诱导 AGS 细胞凋亡。该凋亡过程与 Bax/VDAC1 的上调和 Bcl-2 的下调有关。这些发现提示 VacA p58 通过 VDAC 依赖性和 Bcl-2 家族依赖性途径释放细胞色素 c。
Zotero 插件