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Open Access Green as soon as Postprint is submitted to ZB.
Bid-mediated mitochondrial damage is a key mechanism in glutamate-induced oxidative stress and AIF-dependent cell death in immortalized HT-22 hippocampal neurons.
Cell Death Differ. 18, 282-292 (2011)
Glutamate toxicity involves increases in intracellular calcium levels and enhanced formation of reactive oxygen species (ROS) causing neuronal dysfunction and death in acute and chronic neurodegenerative disorders. The molecular mechanisms mediating glutamate-induced ROS formation are, however, still poorly defined. Using a model system that lacks glutamate-operated calcium channels, we demonstrate that glutamate-induced acceleration of ROS levels occurs in two steps and is initiated by lipoxygenases (LOXs) and then significantly accelerated through Bid-dependent mitochondrial damage. The Bid-mediated secondary boost of ROS formation downstream of LOX activity further involves mitochondrial fragmentation and release of mitochondrial apoptosis-inducing factor (AIF) to the nucleus. These data imply that the activation of Bid is an essential step in amplifying glutamate-induced formation of lipid peroxides to irreversible mitochondrial damage associated with further enhanced free radical formation and AIF-dependent execution of cell death.
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Publication type
Article: Journal article
Document type
Scientific Article
Keywords
Glutamate; Neuronal cell death; Apoptosis; Mitochondria; Lipid peroxidation; Reactive oxygen species; Apoptosis-inducing factor
ISSN (print) / ISBN
1350-9047
e-ISSN
1476-5403
Journal
Cell Death and Differentiation
Quellenangaben
Volume: 18,
Issue: 2,
Pages: 282-292
Publisher
Nature Publishing Group
Non-patent literature
Publications
Reviewing status
Peer reviewed