Document Detail


Effects of docosahexaenoic acid on mouse brain synaptic plasma membrane proteome analyzed by mass spectrometry and (16)O/(18)O labeling.
MedLine Citation:
PMID:  22003853     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Docosahexenoic acid (DHA, 22:6n-3) plays an important role in development of proper brain function in mammals. We have previously reported that DHA promotes synaptogenesis and synaptic function in hippocampal neurons while DHA-depletion in the brain due to n-3 fatty acid deficiency produces opposite effects. To gain insight into underlying molecular mechanisms, we investigated whether the brain DHA status affects the synaptic plasma membrane (SPM) proteome by using nanoLC-ESI-MS/MS and (16)O/(18)O labeling. The DHA level in mouse brains was lowered by dietary depletion of n-3 fatty acids, and SPM was prepared by differential centrifugation followed by osmotic shock. SPM proteins from DHA-adequate and depleted brains were analyzed by nanoLC-ESI-MS/MS after SDS-PAGE, in-gel digestion, and differential O(18)/O(16) labeling. This strategy allowed comparative quantitation of more than 200 distinct membrane or membrane-associated proteins from DHA-adequate or depleted brains. We found that 18 pre- and postsynaptic proteins that are relevant to synaptic physiology were significantly down-regulated in DHA-depleted mouse brains. The protein network analysis suggests involvement of CREB and caspase-3 pathways in the DHA-dependent modulation of synaptic proteome. Reduction of specific synaptic proteins due to brain DHA-depletion may be an important mechanism for the suboptimal brain function associated with n-3 fatty acid deficiency.
Authors:
Vishaldeep K Sidhu; Bill X Huang; Hee-Yong Kim
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, N.I.H., Intramural     Date:  2011-10-26
Journal Detail:
Title:  Journal of proteome research     Volume:  10     ISSN:  1535-3907     ISO Abbreviation:  J. Proteome Res.     Publication Date:  2011 Dec 
Date Detail:
Created Date:  2011-12-05     Completed Date:  2012-03-25     Revised Date:  2013-06-27    
Medline Journal Info:
Nlm Unique ID:  101128775     Medline TA:  J Proteome Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  5472-80     Citation Subset:  IM    
Affiliation:
Laboratory of Molecular Signaling, Division of Intramural Clinical and Biological Reasearch, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland, United States.
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MeSH Terms
Descriptor/Qualifier:
Animals
Blotting, Western
Centrifugation / methods
Cerebral Cortex / chemistry,  drug effects*
Cyclic AMP Response Element-Binding Protein / chemistry
Docosahexaenoic Acids / pharmacology*
Down-Regulation
Electrophoresis, Polyacrylamide Gel
Fatty Acids, Omega-3 / chemistry
Female
Isotope Labeling / methods*
Mass Spectrometry / methods
Membrane Proteins / analysis,  chemistry
Mice
Mice, Inbred C57BL
Osmotic Pressure
Oxygen Isotopes / chemistry
Pregnancy
Proteome / analysis*,  chemistry
Synapses / chemistry
Synaptic Membranes / chemistry,  drug effects*
Grant Support
ID/Acronym/Agency:
ZIA AA000284-21/AA/NIAAA NIH HHS
Chemical
Reg. No./Substance:
0/Creb1 protein, mouse; 0/Cyclic AMP Response Element-Binding Protein; 0/Fatty Acids, Omega-3; 0/Membrane Proteins; 0/Oxygen Isotopes; 0/Proteome; 25167-62-8/Docosahexaenoic Acids
Comments/Corrections

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