Document Detail


Reduced G protein-coupled signaling efficiency in retinal rod outer segments in response to n-3 fatty acid deficiency.
MedLine Citation:
PMID:  15145938     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The fatty acid (FA) docosahexaenoic acid (DHA, 22: 6n-3) is highly enriched in membrane phospholipids of the central nervous system and retina. Loss of DHA because of n-3 FA deficiency leads to suboptimal function in learning, memory, olfactory-based discrimination, spatial learning, and visual acuity. G protein-coupled receptor (GPCR) signal transduction is a common signaling motif in these neuronal pathways. Here we investigated the effect of n-3 FA deficiency on GPCR signaling in retinal rod outer segment (ROS) membranes isolated from rats raised on n-3-adequate or -deficient diets. ROS membranes of second generation n-3 FA-deficient rats had approximately 80% less DHA than n-3-adequate rats. DHA was replaced by docosapentaenoic acid (22:5n-6), an n-6 FA. This replacement correlated with desensitization of visual signaling in n-3 FA-deficient ROS, as evidenced by reduced rhodopsin activation, rhodopsin-transducin (G(t)) coupling, cGMP phosphodiesterase activity, and slower formation of metarhodopsin II (MII) and the MII-G(t) complex relative to n-3 FA-adequate ROS. ROS membranes from n-3 FA-deficient rats exhibited a higher degree of phospholipid acyl chain order relative to n-3 FA-adequate rats. These findings reported here provide an explanation for the reduced amplitude and delayed response of the electroretinogram a-wave observed in n-3 FA deficiency in rodents and nonhuman primates. Because members of the GPCR family are widespread in signaling pathways in the nervous system, the effect of reduced GPCR signaling due to the loss of membrane DHA may serve as an explanation for the suboptimal neural signaling observed in n-3 FA deficiency.
Authors:
Shui-Lin Niu; Drake C Mitchell; Sun-Young Lim; Zhi-Ming Wen; Hee-Yong Kim; Norman Salem; Burton J Litman
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Publication Detail:
Type:  Journal Article     Date:  2004-05-15
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  279     ISSN:  0021-9258     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  2004 Jul 
Date Detail:
Created Date:  2004-07-19     Completed Date:  2004-09-21     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  31098-104     Citation Subset:  IM    
Affiliation:
Laboratory of Membrane Biochemistry and Biophysics, National Institute on Alcohol Abuse and Alcoholism, Rockville, Maryland 20852, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Docosahexaenoic Acids / metabolism
Electroretinography
Eye Proteins / metabolism*
Fatty Acids, Omega-3 / metabolism*
Female
Heterotrimeric GTP-Binding Proteins / metabolism*
Membrane Lipids / metabolism
Phosphoric Diester Hydrolases / metabolism
Rats
Rats, Long-Evans
Rod Cell Outer Segment / metabolism*
Signal Transduction
Chemical
Reg. No./Substance:
0/Eye Proteins; 0/Fatty Acids, Omega-3; 0/GNAT1 protein, human; 0/Gnat1 protein, rat; 0/Membrane Lipids; 25167-62-8/Docosahexaenoic Acids; EC 3.1.4.-/Phosphoric Diester Hydrolases; EC 3.6.5.1/Heterotrimeric GTP-Binding Proteins

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