|
rdf:type |
|
|
lifeskim:mentions |
|
|
pubmed:issue |
2
|
|
pubmed:dateCreated |
2004-1-15
|
|
pubmed:abstractText |
Beta-amyloid (betaA) peptide is strongly implicated in the neurodegeneration underlying Alzheimer's disease, but the mechanisms of neurotoxicity remain controversial. This study establishes a central role for oxidative stress by the activation of NADPH oxidase in astrocytes as the cause of betaA-induced neuronal death. betaA causes a loss of mitochondrial potential in astrocytes but not in neurons. The mitochondrial response consists of Ca2+-dependent transient depolarizations superimposed on a slow collapse of potential. The slow response is both prevented by antioxidants and, remarkably, reversed by provision of glutamate and other mitochondrial substrates to complexes I and II. These findings suggest that the depolarization reflects oxidative damage to metabolic pathways upstream of mitochondrial respiration. Inhibition of NADPH oxidase by diphenylene iodonium or 4-hydroxy-3-methoxy-acetophenone blocks betaA-induced reactive oxygen species generation, prevents the mitochondrial depolarization, prevents betaA-induced glutathione depletion in both neurons and astrocytes, and protects neurons from cell death, placing the astrocyte NADPH oxidase as a primary target of betaA-induced neurodegeneration.
|
|
pubmed:language |
eng
|
|
pubmed:journal |
|
|
pubmed:citationSubset |
IM
|
|
pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Amyloid beta-Peptides,
http://linkedlifedata.com/resource/pubmed/chemical/Calcium,
http://linkedlifedata.com/resource/pubmed/chemical/Glutathione,
http://linkedlifedata.com/resource/pubmed/chemical/Ion Channels,
http://linkedlifedata.com/resource/pubmed/chemical/Mitochondrial Membrane Transport...,
http://linkedlifedata.com/resource/pubmed/chemical/NADPH Oxidase,
http://linkedlifedata.com/resource/pubmed/chemical/Peptide Fragments,
http://linkedlifedata.com/resource/pubmed/chemical/Reactive Oxygen Species,
http://linkedlifedata.com/resource/pubmed/chemical/amyloid beta-protein (1-42),
http://linkedlifedata.com/resource/pubmed/chemical/amyloid beta-protein (25-35),
http://linkedlifedata.com/resource/pubmed/chemical/mitochondrial permeability...
|
|
pubmed:status |
MEDLINE
|
|
pubmed:month |
Jan
|
|
pubmed:issn |
1529-2401
|
|
pubmed:author |
|
|
pubmed:issnType |
Electronic
|
|
pubmed:day |
14
|
|
pubmed:volume |
24
|
|
pubmed:owner |
NLM
|
|
pubmed:authorsComplete |
Y
|
|
pubmed:pagination |
565-75
|
|
pubmed:dateRevised |
2010-11-18
|
|
pubmed:meshHeading |
pubmed-meshheading:14724257-Amyloid beta-Peptides,
pubmed-meshheading:14724257-Animals,
pubmed-meshheading:14724257-Astrocytes,
pubmed-meshheading:14724257-Calcium,
pubmed-meshheading:14724257-Cell Death,
pubmed-meshheading:14724257-Cells, Cultured,
pubmed-meshheading:14724257-Enzyme Activation,
pubmed-meshheading:14724257-Glutathione,
pubmed-meshheading:14724257-Ion Channels,
pubmed-meshheading:14724257-Membrane Potentials,
pubmed-meshheading:14724257-Mitochondria,
pubmed-meshheading:14724257-Mitochondrial Membrane Transport Proteins,
pubmed-meshheading:14724257-NADPH Oxidase,
pubmed-meshheading:14724257-Neurons,
pubmed-meshheading:14724257-Oxidative Stress,
pubmed-meshheading:14724257-Peptide Fragments,
pubmed-meshheading:14724257-Rats,
pubmed-meshheading:14724257-Rats, Sprague-Dawley,
pubmed-meshheading:14724257-Reactive Oxygen Species
|
|
pubmed:year |
2004
|
|
pubmed:articleTitle |
Beta-amyloid peptides induce mitochondrial dysfunction and oxidative stress in astrocytes and death of neurons through activation of NADPH oxidase.
|
|
pubmed:affiliation |
Mitochondrial Biology Group, Department of Physiology, University College London, London WC1E 6BT, United Kingdom.
|
|
pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
|
