title: Protein disulfide isomerase knockdown-induced cell death is cell-line-dependent and involves apoptosis in MCF-7 cells.
abstract: 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.
authors.affiliation: Graduate School of Biomedical Sciences, Hiroshima University, Minami-ku, Hiroshima, Japan.
authors.forename: Tomoyo
authors.initials: T
authors.lastname: Hashida
authors.forename: Yaichiro
authors.initials: Y
authors.lastname: Kotake
authors.forename: Shigeru
authors.initials: S
authors.lastname: Ohta
mesh_terms: D017209:Apoptosis / Q000235:genetics* / Q000502:physiology; D020169:Caspases / Q000378:metabolism / Q000502:physiology; D045744:Cell Line, Tumor; D055785:Gene Knockdown Techniques; D006801:Humans; D019704:Protein Disulfide-Isomerases / Q000235:genetics* / Q000502:physiology*; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology
chemical_list: D020169:Caspases; D019704:Protein Disulfide-Isomerases