ABSTRACT 2 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 4Yhydroxylase (p4HD), and an esTrogen and Thyroid hormoneY binding proTein. previous reporTs indicaTe ThaT some endocrineYdisrupTing chemicals (EDCs) bind To pDI and disTurb iTs funcTions, and we execuTed pDIYknockdown To examine The effecTs of dysfuncTion of pDI. In This sTudy, The effecTs of pDIYknockdown were compared among Three cell lines: MCFY7, SHYSY5Y and HeLa. pDIYknockdown induced differenT levels of cyToToxiciTy among These cell lines. In MCFY7 cells, pDIYknockdown acTivaTed apopToTic signaling, causing cyTochrome c release from miTochondria and acTivaTion of caspaseY9, caspaseY6, caspaseY7 and poly [ADpYribose] polymeraseY1, and The cyToToxiciTy induced by pDIYknockdown was suppressed by a panYcaspase inhibiTor, zYVADYfmk. these daTa suggesT ThaT cell deaTh induced by pDIYknockdown is caspaseYdependenT apopTosis in MCFY7 cells.