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During prolonged ER stress, IRE1, PERK, and ATF6 may induce pro-apoptotic signaling through activation of C/EBP homologous protein (CHOP), which subsequently leads to the initiation of ER stress-mediated apoptosis through regulation of Bcl-2 family members (Wongprayoon and Govitrapong (2017) suggested that METH-induced apoptotic death is mediated (at least in part) through an ER-dependent mechanism involving CHOP, spliced X-box binding protein 1 (XBP1), caspase-12, and caspase-3 in vitro