title: Endoplasmic reticulum (ER) stress inhibitor salubrinal protects against ceramide-induced SH-SY5Y cell death.
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.
authors.affiliation: Department of Cardiology, The First Affiliated Hospital, Nanjing Medical University, Nanjing 210024, Jiangsu, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Gong
authors.forename: Qin
authors.initials: Q
authors.lastname: Wang
authors.forename: Zheng
authors.initials: Z
authors.lastname: Lin
authors.forename: Ming-long
authors.initials: ML
authors.lastname: Chen
authors.forename: Guo-zhen
authors.initials: GZ
authors.lastname: Sun
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D002518:Ceramides / Q000494:pharmacology; D002934:Cinnamates / Q000494:pharmacology*; D019610:Cytoprotection; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects*; D004722:Endoribonucleases / Q000378:metabolism; D006801:Humans; D048670:MAP Kinase Kinase 4 / Q000378:metabolism; D048848:MAP Kinase Kinase Kinase 5 / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D034741:RNA, Small Interfering / Q000096:biosynthesis; D013890:Thiourea / Q000031:analogs & derivatives* / Q000494:pharmacology; D051742:Transcription Factor CHOP / Q000378:metabolism
chemical_list: D002518:Ceramides; D002934:Cinnamates; C497249:DDIT3 protein, human; D034741:RNA, Small Interfering; C496827:salubrinal; D051742:Transcription Factor CHOP; C528229:ERN1 protein, human; D017346:Protein Serine-Threonine Kinases; D048848:MAP Kinase Kinase Kinase 5; C482858:MAP3K5 protein, human; D048670:MAP Kinase Kinase 4; D004722:Endoribonucleases; C504327:N-(alpha-hydroxyoctadecanoyl)phytosphingosine; D013890:Thiourea