Document Detail


Bid-mediated mitochondrial damage is a key mechanism in glutamate-induced oxidative stress and AIF-dependent cell death in immortalized HT-22 hippocampal neurons.
MedLine Citation:
PMID:  20689558     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
S Tobaben; J Grohm; A Seiler; M Conrad; N Plesnila; C Culmsee
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-08-06
Journal Detail:
Title:  Cell death and differentiation     Volume:  18     ISSN:  1476-5403     ISO Abbreviation:  Cell Death Differ.     Publication Date:  2011 Feb 
Date Detail:
Created Date:  2011-01-10     Completed Date:  2011-04-25     Revised Date:  2013-05-29    
Medline Journal Info:
Nlm Unique ID:  9437445     Medline TA:  Cell Death Differ     Country:  England    
Other Details:
Languages:  eng     Pagination:  282-92     Citation Subset:  IM    
Affiliation:
Institute for Pharmacology and Toxicology, Philipps University Marburg, Karl-von-Frisch-Strasse 1, Marburg, Germany.
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MeSH Terms
Descriptor/Qualifier:
Apoptosis
Apoptosis Inducing Factor / metabolism*
BH3 Interacting Domain Death Agonist Protein / antagonists & inhibitors,  metabolism*
Cell Line, Transformed
Glutamic Acid / toxicity*
Hippocampus / cytology
Humans
Lipoxygenase Inhibitors / pharmacology
Lipoxygenases / chemistry,  metabolism
Mitochondria / metabolism*
Neurons / cytology,  metabolism*
Oxidative Stress
Reactive Oxygen Species / metabolism
Chemical
Reg. No./Substance:
0/Apoptosis Inducing Factor; 0/BH3 Interacting Domain Death Agonist Protein; 0/Lipoxygenase Inhibitors; 0/Reactive Oxygen Species; 56-86-0/Glutamic Acid; EC 1.13.11.-/Lipoxygenases
Comments/Corrections

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