Biomaterial Database

Amyloid beta-protein potentiates tunicamycin-induced neuronal death in organotypic hippocampal slice cultures. 2007

T Imai, and Y Kosuge, and K Ishige, and Y Ito

Research Unit of Pharmacology, Department of Clinical Pharmacy, College of Pharmacy, Nihon University, 7-7-1 Narashinodai, Funabashi-shi, Chiba 274-8555, Japan.

We have assessed amyloid beta protein (Abeta)-induced neurotoxicity, with and without added tunicamycin (TM), an inhibitor of N-glycosylation in the endoplasmic reticulum (ER), in rat organotypic hippocampal slice cultures (OHCs). In the rat OHCs cultured for 3 weeks, there was little neurotoxicity after treatment with Abeta(25-35) (25 microM) alone for 48 h. However, with TM alone, concentration-dependent neuronal death was observed at concentrations between 20 and 80 microg/mL. When amyloid-beta protein was combined with tunicamycin (Abeta+TM), cell death was more acute than with TM alone. Western blot analysis revealed that calpain activity and the active forms of caspase-12 and caspase-3 was increased after exposure to Abeta+TM as compared with exposure to TM alone. In contrast, the levels of glucose regulated protein (GRP)94, GRP78 and C/EBP homologous protein (CHOP) were not changed in the presence of Abeta. Abeta potentiation of TM neurotoxicity was reversibly blocked by S-allyl-L-cysteine (SAC), an organosulfur compound purified from aged garlic extract, and the L-type calcium channel blocker, nifedipine, in a restricted neuronal area of the OHCs. Simultaneously applied SAC also reversed the increases in calpain activity and the active forms of caspase-12 and caspase-3 by Abeta+TM with no change in the increased levels of GRP94, GRP78 and CHOP. These data indicate that Abeta facilitates the calpain-caspase-12-caspase-3 pathway, thus potentiating TM-induced neuronal death in the hippocampus.

UI	MeSH Term	Description	Entries
D009474	Neurons	The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the NERVOUS SYSTEM.	Nerve Cells,Cell, Nerve,Cells, Nerve,Nerve Cell,Neuron
D009924	Organ Culture Techniques	A technique for maintenance or growth of animal organs in vitro. It refers to three-dimensional cultures of undisaggregated tissue retaining some or all of the histological features of the tissue in vivo. (Freshney, Culture of Animal Cells, 3d ed, p1)	Organ Culture,Culture Technique, Organ,Culture Techniques, Organ,Organ Culture Technique,Organ Cultures
D010446	Peptide Fragments	Partial proteins formed by partial hydrolysis of complete proteins or generated through PROTEIN ENGINEERING techniques.	Peptide Fragment,Fragment, Peptide,Fragments, Peptide
D002452	Cell Count	The number of CELLS of a specific kind, usually measured per unit volume or area of sample.	Cell Density,Cell Number,Cell Counts,Cell Densities,Cell Numbers,Count, Cell,Counts, Cell,Densities, Cell,Density, Cell,Number, Cell,Numbers, Cell
D004305	Dose-Response Relationship, Drug	The relationship between the dose of an administered drug and the response of the organism to the drug.	Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D004357	Drug Synergism	The action of a drug in promoting or enhancing the effectiveness of another drug.	Drug Potentiation,Drug Augmentation,Augmentation, Drug,Augmentations, Drug,Drug Augmentations,Drug Potentiations,Drug Synergisms,Potentiation, Drug,Potentiations, Drug,Synergism, Drug,Synergisms, Drug
D005786	Gene Expression Regulation	Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation.	Gene Action Regulation,Regulation of Gene Expression,Expression Regulation, Gene,Regulation, Gene Action,Regulation, Gene Expression
D006624	Hippocampus	A curved elevation of GRAY MATTER extending the entire length of the floor of the TEMPORAL HORN of the LATERAL VENTRICLE (see also TEMPORAL LOBE). The hippocampus proper, subiculum, and DENTATE GYRUS constitute the hippocampal formation. Sometimes authors include the ENTORHINAL CORTEX in the hippocampal formation.	Ammon Horn,Cornu Ammonis,Hippocampal Formation,Subiculum,Ammon's Horn,Hippocampus Proper,Ammons Horn,Formation, Hippocampal,Formations, Hippocampal,Hippocampal Formations,Hippocampus Propers,Horn, Ammon,Horn, Ammon's,Proper, Hippocampus,Propers, Hippocampus,Subiculums
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D000831	Animals, Newborn	Refers to animals in the period of time just after birth.	Animals, Neonatal,Animal, Neonatal,Animal, Newborn,Neonatal Animal,Neonatal Animals,Newborn Animal,Newborn Animals