Graduate School of Biomedical Sciences, Hiroshima University, Minami-ku, Hiroshima, Japan.
J Toxicol Sci. 2011 Jan;36(1):1-7. doi: 10.2131/jts.36.1.
Protein disulfide isomerase (PDI) is a multifunctional protein that catalyzes disulfide bond formation and assists protein folding, as well as being a structural subunit of microsomal triglyceride transfer protein (MTP) and prolyl 4-hydroxylase (P4HD), and an estrogen and thyroid hormone-binding protein. Previous reports indicate that some endocrine-disrupting chemicals (EDCs) bind to PDI and disturb its functions, and we executed PDI-knockdown to examine the effects of dysfunction of PDI. In this study, the effects of PDI-knockdown were compared among three cell lines: MCF-7, SH-SY5Y and HeLa. PDI-knockdown induced different levels of cytotoxicity among these cell lines. In MCF-7 cells, PDI-knockdown activated apoptotic signaling, causing cytochrome c release from mitochondria and activation of caspase-9, caspase-6, caspase-7 and poly[ADP-ribose]polymerase-1, and the cytotoxicity induced by PDI-knockdown was suppressed by a pan-caspase inhibitor, z-VAD-fmk. These data suggest that cell death induced by PDI-knockdown is caspase-dependent apoptosis in MCF-7 cells.
蛋白质二硫键异构酶（PDI）是一种多功能蛋白，可催化二硫键形成并协助蛋白质折叠，同时作为微粒体甘油三酯转移蛋白（MTP）和脯氨酰 4-羟化酶（P4HD）的结构亚基，以及雌激素和甲状腺激素结合蛋白。先前的报告表明，一些内分泌干扰化学物质（EDCs）与 PDI 结合并扰乱其功能，我们执行了 PDI 敲低实验以检查 PDI 功能障碍的影响。在这项研究中，我们比较了 PDI 敲低对三种细胞系（MCF-7、SH-SY5Y 和 HeLa）的影响。PDI 敲低在这些细胞系中诱导了不同程度的细胞毒性。在 MCF-7 细胞中，PDI 敲低激活了凋亡信号，导致细胞色素 c 从线粒体释放并激活 caspase-9、caspase-6、caspase-7 和多聚[ADP-核糖]聚合酶-1，PDI 敲低诱导的细胞毒性被泛半胱天冬酶抑制剂 z-VAD-fmk 抑制。这些数据表明，PDI 敲低诱导的细胞死亡是 MCF-7 细胞中依赖半胱天冬酶的凋亡。
