Comparative study of endoplasmic reticulum stress-induced neuronal death in rat cultured hippocampal and cerebellar granule neurons.
In this study, experiments were performed to characterize further the pathways responsible for neuronal death induced by endoplasmic reticulum (ER) stress in cultured hippocampal neurons (HPN) and cerebellar granule neurons (CGN) using tunicamycin (TM) and amyloid beta-peptide (Abeta). Exposure of HPN to Abeta or TM resulted in a time-dependent increase in the expression of 78-kDa glucose-regulated protein (GRP78) and caspase-12, an ER-resident caspase. In contrast, in CGN, although a drastic increase in the expression of GRP78 was found as was the case in HPN, no up-regulation of caspase-12 was detected. These results were consistent with immunohistochemical results that there were far lower number of caspase-12-positive cells in the cerebellum than in the cerebral cortex and hippocampus, and that caspase-12-positive cells were not identified in the external granule cell layer of the cerebellum of P7 rats. In CGN, a significant increase in the expression of C/EBP homologous protein (CHOP) protein was detected after exposure to Abeta or TM, whereas no such an increase in the protein expression was observed in HPN. In addition, S-allyl-L-cysteine (SAC), an organosulfur compound purified from aged garlic extract, protected neurons against TM-induced neurotoxicity in HPN but not in CGN, as in the case of Abeta-induced neurotoxicity. These results suggest that the pathway responsible for neuronal death induced by Abeta and TM in HPN differs from that in CGN, and that a caspase-12-dependent pathway is involved in HPN while a CHOP-dependent pathway is involved in CGN in ER stress-induced neuronal death.
Department of Pharmacology, College of Pharmacy, Nihon University, Funabashi 274-8555, Japan.
Yasuhiro
Y
Kosuge
Taeko
T
Sakikubo
Kumiko
K
Ishige
Yoshihisa
Y
Ito
D000818:Animals; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D002470:Cell Survival / Q000502:physiology; D002478:Cells, Cultured; D002531:Cerebellum / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D004721:Endoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D014415:Tunicamycin / Q000633:toxicity
D014415:Tunicamycin