title: The endoplasmic reticulum-related events in S-nitrosoglutathione-induced neurotoxicity in cerebellar granule cells.
abstract: Nitric oxide (NO)-induced neurotoxicities are involved in the pathogenesis of several neurodegenerative disorders featured by misfolded proteins. However, the details remain to be investigated. In the present work, we focus on the study of some endoplasmic reticulum-related events in S-nitrosoglutathione (GSNO)-induced neurotoxicity in cerebellar granule cells (CGCs) and we demonstrated that: (1) GSNO caused sustained elevation of intracellular calcium; (2) This calcium elevation resulted partially from the depletion of endoplasmic reticulum (ER) calcium stores; (3) There was ER stress which was indicated by the incomplete splicing of X-box binding protein (XBP-1) mRNA by 8-polysialyltransferase (Pst1); (4) GSNO upregulated the expression of the proapoptotic growth arrest and DNA damage-inducible gene (Gadd153) and caused the depletion of intracellular glutathione (GSH) pools. At the same time, GSNO downregulated the expression of the antiapoptotic gene Sarco/endoplasmic reticulum calcium-ATPase (SERCA2b) in parallel with the downregulation of the antiapoptotic ER chaperones-glucose-regulated protein genes (Grp78 and Grp94). These effects indicate that ER is one of the NO targets in GSNO-induced neurotoxicity in cerebellar granule cells besides mitochondria.
authors.affiliation: Center for Molecular Biology, Institute of Biophysics, Chinese Academy of Sciences, P.O. Box 33, 15 Datun Road, Chaoyang District, Beijing 100101, PR China.
authors.forename: Jie
authors.initials: J
authors.lastname: He
authors.forename: Hongjun
authors.initials: H
authors.lastname: Kang
authors.forename: Fang
authors.initials: F
authors.lastname: Yan
authors.forename: Chang
authors.initials: C
authors.lastname: Chen
mesh_terms: D000818:Animals; D022762:CCAAT-Enhancer-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D002470:Cell Survival; D002478:Cells, Cultured; D002526:Cerebellar Diseases / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D002531:Cerebellum / Q000473:pathology; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D005786:Gene Expression Regulation; D005978:Glutathione / Q000235:genetics / Q000378:metabolism*; D006706:Homeostasis; D007424:Intracellular Fluid / Q000378:metabolism; D009474:Neurons / Q000378:metabolism*; D009498:Neurotoxins; D009569:Nitric Oxide / Q000378:metabolism; D011487:Protein Conformation; D011499:Protein Processing, Post-Translational / Q000502:physiology*; D012326:RNA Splicing; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D026422:S-Nitrosoglutathione; D013312:Stress, Physiological / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism; D051742:Transcription Factor CHOP; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D022762:CCAAT-Enhancer-Binding Proteins; C497251:Ddit3 protein, rat; D009498:Neurotoxins; D012333:RNA, Messenger; D014157:Transcription Factors; D051742:Transcription Factor CHOP; D009569:Nitric Oxide; D026422:S-Nitrosoglutathione; D005978:Glutathione; D002118:Calcium