A key role for the microglial NADPH oxidase in APP-dependent killing of neurons

Autor: Karl-Heinz Krause, Bin Qin, Lena Serrander, Bin Li, Laetitia Cartier, Michel Dubois-Dauphin
Rok vydání: 2005
Předmět:
Aging
Phagocyte
Alzheimer Disease/ physiopathology
Cell Culture Techniques
Cell Count
Ascorbic Acid
ddc:616.07
Antioxidants
Onium Compounds/pharmacology
Amyloid beta-Protein Precursor
Onium Compounds
Transduction
Genetic
Amyloid precursor protein
Vitamin E
Enzyme Inhibitors
Ascorbic Acid/pharmacology
Enzyme Inhibitors/pharmacology
Neurons
NADPH oxidase
Microglia
biology
Cell Death
General Neuroscience
Amyloid beta-Protein Precursor/ metabolism
Cell cycle
Cell biology
medicine.anatomical_structure
Programmed cell death
Blotting
Western
Receptors
Cell Surface
Reactive Oxygen Species/metabolism
Alzheimer Disease
Macrophages/metabolism
Neuroblastoma
Cell Line
Tumor
mental disorders
medicine
Humans
Vitamin E/pharmacology
Microglia/drug effects/metabolism
Macrophages
NADPH Oxidases
Neurons/ cytology/drug effects/metabolism
medicine.disease
Protease Nexins
Antioxidants/pharmacology
Microscopy
Fluorescence
Cell culture
Immunology
Mutation
biology.protein
NADPH Oxidase/deficiency/ metabolism
Neurology (clinical)
Geriatrics and Gerontology
Receptors
Cell Surface/ metabolism
Reactive Oxygen Species
Developmental Biology
Zdroj: Neurobiology of Aging, Vol. 27, No 11 (2006) pp. 1577-1587
ISSN: 1558-1497
0197-4580
Popis: Reactive oxygen species (ROS) and deposition of cleaved products of amyloid precursor protein (APP) are thought to contribute to neuronal loss observed in Alzheimer's disease (AD). The relationship between these factors was studied in a neuroblastoma and microglia co-culture system. Overexpression of wild-type APP (APP-wt) or APP with three mutations typical of familial AD (APP-3m) in SH-SY5Y neuroblastoma cells did not directly alter their morphology, growth rate, cell cycle or H(2)O(2) sensitivity. In a co-culture of APP-wt neuroblastoma cells with microglia, microglial cells generated ROS and neuronal cells died. The cell death was more pronounced in APP-3m-expressing neurons. Neuroblastoma cell death was attenuated by ROS-scavengers and was dose-dependently inhibited by the NADPH oxidase inhibitor diphenyleneiodonium chloride (DPI). Macrophage cell lines behaved similarly to microglia in the co-culture model. However, a macrophage cell line deficient in the NADPH oxidase subunit, gp91phox, failed to kill neurons. These results suggest that APP-dependent microglia activation and subsequent ROS generation by the phagocyte NADPH oxidase play a crucial role in neuronal killing in a cellular model of AD.
Databáze: OpenAIRE
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