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Tobaben, S.* ; Grohm, J.* ; Seiler, A. ; Conrad, M. ; Plesnila, N.* ; Culmsee, C.*

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)
Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
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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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Glutamate; Neuronal cell death; Apoptosis; Mitochondria; Lipid peroxidation; Reactive oxygen species; Apoptosis-inducing factor
ISSN (print) / ISBN 1350-9047
e-ISSN 1476-5403
Quellenangaben Band: 18, Heft: 2, Seiten: 282-292 Artikelnummer: , Supplement: ,
Verlag Nature Publishing Group
Begutachtungsstatus Peer reviewed