Article ID Journal Published Year Pages File Type
1929119 Biochemical and Biophysical Research Communications 2012 5 Pages PDF
Abstract

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.

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