Background: Salubrinal, which inhibits the dephosphorylation of eukaryotic translation initiation factor 2 subunit α (eIF2α), protects against cadmium toxicity. However, the underlying mechanisms of salubrinal concerning endoplasmic reticulum (ER) stress and autophagy in SH-SY5Y human neuroblastoma cells following exposure to cadmium remain unknown. Methods: Cells were exposed to 1.0 μmol/L CdCl2 and 10 μmol/L salubrinal for 24 h. Cytotoxicity was evaluated using WST-8 assays. ER stress- and autophagy-related genes were analyzed by PCR and immunoblotting. To evaluate lysosomal pH and autophagosome formation, fluorescence signals were detected using confocal laser scanning microscopy. Flux assays were performed to distinguish autophagic impairment from autophagic activation. Results: Salubrinal suppressed cadmium-induced cell death. Treatment with salubrinal led to increased levels of phosphorylated eIF2α and GRP78 and a decrease in the mRNA level of CHOP in cadmium-exposed cells. p62 and LC3B-II levels increased in cells treated with both cadmium and salubrinal. Flux assays revealed that the increase in LC3B-II expression was impaired by treatment with cadmium and enhanced by salubrinal treatment. Conclusions: Salubrinal suppressed cadmium-induced CHOP expression and activated autophagic flux, thereby promoting cell survival.
Takamitsu Miyayama (Sat,) studied this question.