Document Detail

Adaptation of neuronal cells to chronic oxidative stress is associated with altered cholesterol and sphingolipid homeostasis and lysosomal function.
MedLine Citation:
PMID:  19712059     Owner:  NLM     Status:  MEDLINE    
Chronic oxidative stress has been causally linked to several neurodegenerative disorders. As sensitivity for oxidative stress greatly differs between brain regions and neuronal cell types, specific cellular mechanisms of adaptation to chronic oxidative stress should exist. Our objective was to identify molecular mechanisms of adaptation of neuronal cells after applying chronic sublethal oxidative stress. We demonstrate that cells resistant to oxidative stress exhibit altered cholesterol and sphingomyelin metabolisms. Stress-resistant cells showed reduced levels of molecules involved in cholesterol trafficking and intracellular accumulation of cholesterol, cholesterol precursors, and metabolites. Moreover, stress-resistant cells exhibited reduced SMase activity. The altered lipid metabolism was associated with enhanced autophagy. Treatment of stress-resistant cells with neutral SMase reversed the stress-resistant phenotype, whereas it could be mimicked by treatment of neuronal cells with a specific inhibitor of neutral SMase. Analysis of hippocampal and cerebellar tissue of mouse brains revealed that the obtained cell culture data reflect the in vivo situation. Stress-resistant cells in vitro showed similar features as the less vulnerable cerebellum in mice, whereas stress-sensitive cells resembled the highly sensitive hippocampal area. These findings suggest an important role of the cell type-specific lipid profile for differential vulnerabilities of different brain areas toward chronic oxidative stress.
Angela B Clement; Martin Gamerdinger; Irfan Y Tamboli; Dieter Lütjohann; Jochen Walter; Isabell Greeve; Gerald Gimpl; Christian Behl
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-08-27
Journal Detail:
Title:  Journal of neurochemistry     Volume:  111     ISSN:  1471-4159     ISO Abbreviation:  J. Neurochem.     Publication Date:  2009 Nov 
Date Detail:
Created Date:  2009-10-20     Completed Date:  2009-11-06     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  2985190R     Medline TA:  J Neurochem     Country:  England    
Other Details:
Languages:  eng     Pagination:  669-82     Citation Subset:  IM    
Institute for Pathobiochemistry, University-Medical Center, Johannes Gutenberg-University Mainz, Germany.
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MeSH Terms
Adaptation, Physiological / drug effects,  physiology*
Autophagy / drug effects
Cell Survival / drug effects
Cerebellum / cytology,  drug effects,  metabolism
Cholesterol / metabolism*
Clone Cells
Gene Expression Regulation / drug effects
Hippocampus / cytology
Hydrogen Peroxide / pharmacology
Lysosomes / drug effects,  metabolism*
Neurons / drug effects,  ultrastructure*
Oxidative Stress / drug effects,  physiology*
Sphingomyelins / metabolism*
Statistics as Topic
Reg. No./Substance:
0/Sphingomyelins; 57-88-5/Cholesterol; 7722-84-1/Hydrogen Peroxide

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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