title: Role of caspase-12 in amyloid beta-peptide-induced toxicity in organotypic hippocampal slices cultured for long periods.
abstract: Amyloid beta (Abeta) toxicity has been implicated in cell death in the hippocampus, but its specific mechanisms are poorly understood. In this study, Abeta-induced cell death was investigated in organotypic hippocampal slice cultures (OHCs) that were cultured for various periods in vitro. There were no obvious histological differences among slices cultured for 3 to 7 weeks in vitro. Although there was little neurotoxicity after treatment with Abeta25-35 in OHCs cultured for relatively shorter periods (3-5 weeks), age-dependent cell death was evident in OHCs cultured for relatively longer periods (6-7 weeks) after exposure to Abeta25-35. In OHCs cultured for 7 weeks, S-allyl-L-cysteine (SAC), a component of aged garlic extract, protected the cells in areas CA1 and CA3 and the dentate gyrus from Abeta25-35-induced toxicity. The immunoreactivity of cleaved caspase-12 was increased whereas that of glucose-regulated protein 78 was not altered after exposure to Abeta25-35. The increases in the cleaved caspase-12 were also reversed by simultaneously applied SAC. These results suggest that OHCs cultured for relatively longer periods are more susceptible to Abeta-induced toxicity and that the Abeta-induced cell death involves caspase-12-dependent pathways. It is also suggested that SAC is able to protect against the Abeta-induced neuronal cell death through the inhibition of the caspase-12-dependent pathway.
authors: Research Unit of Pharmacology, College of Pharmacy, Nihon University, Funabashi, Japan.
authors: Kumiko
authors: K
authors: Ishige
authors: Noritaka
authors: N
authors: Takagi
authors: Toru
authors: T
authors: Imai
authors: Wolf Dieter
authors: WD
authors: Rausch
authors: Yasuhiro
authors: Y
authors: Kosuge
authors: Tetsuroh
authors: T
authors: Kihara
authors: Kuniko
authors: K
authors: Kusama-Eguchi
authors: Hiroko
authors: H
authors: Ikeda
authors: Alexander Rudolf
authors: AR
authors: Cools
authors: John Lionel
authors: JL
authors: Waddington
authors: Noriaki
authors: N
authors: Koshikawa
authors: Yoshihisa
authors: Y
authors: Ito
mesh_terms: D016229:Amyloid beta-Peptides / Q000494:pharmacology*; D000818:Animals; D015153:Blotting, Western; D053454:Caspase 12 / Q000378:metabolism* / Q000502:physiology; D002470:Cell Survival / Q000187:drug effects; D003545:Cysteine / Q000031:analogs & derivatives / Q000494:pharmacology; D018891:Dentate Gyrus / Q000187:drug effects* / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D004721:Endoplasmic Reticulum / Q000187:drug effects / Q000201:enzymology; D000091342:Endoplasmic Reticulum Chaperone BiP; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D006360:Heat-Shock Proteins / Q000378:metabolism; D007051:Ibotenic Acid / Q000494:pharmacology; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D018832:Molecular Chaperones / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000473:pathology; D009924:Organ Culture Techniques; D010446:Peptide Fragments / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
chemical_list: D016229:Amyloid beta-Peptides; D000091342:Endoplasmic Reticulum Chaperone BiP; D018690:Excitatory Amino Acid Agonists; C051684:GRP78 protein, rat; D006360:Heat-Shock Proteins; D018832:Molecular Chaperones; D010446:Peptide Fragments; C074636:amyloid beta-protein (25-35); C113041:amyloid beta-protein (35-25); D007051:Ibotenic Acid; C065299:S-allylcysteine; D007770:L-Lactate Dehydrogenase; D053454:Caspase 12; D003545:Cysteine