Salubrinal suppresses cadmium-induced cell death by affecting endoplasmic reticulum stress/autophagy in SH-SY5Y human neuroblastoma cells

Background: Salubrinal, inhibits the dephosphorylation of eukaryotic translation initiation factor 2 subunit α (eIF2α), provides protection against cadmium toxicity. However, underlying mechanisms of salubrinal for ER stress/autophagy remain unknown in SH-SY5Y human neuroblastoma cells following exposure to cadmium. Methods: Cells were exposed to 1.0 µM CdCl 2 and 10 µM salubrinal for 24 h. Cytotoxicities and viabilities were evaluated by using a WST-8 assay. The expression of ER stress– and autophagy–related genes was analyzed by immunoblotting. To evaluate lysosomal pH and autophagosomal formation, fluorescence signals of LysoTracker and Cyto-ID were determined by confocal laser scanning microscopy, respectively. To discriminate autophagic impairment or autophagic activation, flux assay was performed with bafilomycin A1. Results: Salubrinal suppressed cadmium-induced cell death. Treatment with salubrinal led to increased levels of phosphorylated eIF2α and 78-kDa glucose-regulated protein and a decrease in mRNA level of CCAAT/enhancer-binding protein homologous protein (CHOP) in cells exposed to cadmium. p62 protein and microtubule-associated protein light chain 3B-II (LC3B-II) was increased in cells treated with both cadmium and salubrinal. Flux assays showed that the increase in LC3B-II expression was enhanced by treatment with salubrinal and bafilomycin A1. Conclusions: Salubrinal suppresses cadmium-induced CHOP expression and activates autophagic flux, thereby promoting cell survival.