Endoplasmic reticulum (ER) stress inhibitor salubrinal protects against ceramide-induced SH-SY5Y cell death

In the present study, we examined the mechanisms of ceramide-induced cell death in SH-SY5Y human neuroblastoma cells. Our results demonstrate a significant endoplasmic reticulum (ER) stress response in SH-SY5Y cells after short-chain ceramide (C6) treatment. Administration of ceramide (C6) to SH-SY5Y human neuroblastoma cells caused apoptotic cell death, which was inhibited by ER stress inhibitor salubrinal. Further, ceramide-induced cell death reduced significantly in stable SH-SY5Y cells expressing C/EBP homologous protein (CHOP) shRNA. Salubrinal inhibited ceramide-induced inositol-requiring enzyme 1α (IRE1α)/apoptosis signal regulating kinase 1 (ASK1)/c-Jun N-terminal kinase (JNK) phosphorylation. Taken together, these data suggest that ceramide-induced SH-SY5Y cell death may be linked to the ER stress-regulated intrinsic pathway, and proposed the potential protective effects of salubrinal.

► Short-chain ceramide (C6) induces ER stress response in SH-SY5Y cells.
► ER stress inhibitor salubrinal protects against ceramide (C6)-induced SH-SY5Y cell death.
► CHOP RNAi knockdown cells are resistant to ceramide (C6).
► Salubrinal inhibits ceramide (C6)-induced IRE1α-ASK1-JNK phosphorylation.