| Reduced G protein-coupled signaling efficiency in retinal rod outer segments in response to n-3 fatty acid deficiency. | |
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MedLine Citation:
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PMID: 15145938 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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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:
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Type: Journal Article Date: 2004-05-15 |
Journal Detail:
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Title: The Journal of biological chemistry Volume: 279 ISSN: 0021-9258 ISO Abbreviation: J. Biol. Chem. Publication Date: 2004 Jul |
Date Detail:
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Created Date: 2004-07-19 Completed Date: 2004-09-21 Revised Date: 2009-11-19 |
Medline Journal Info:
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Nlm Unique ID: 2985121R Medline TA: J Biol Chem Country: United States |
Other Details:
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Languages: eng Pagination: 31098-104 Citation Subset: IM |
Affiliation:
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Laboratory of Membrane Biochemistry and Biophysics, National Institute on Alcohol Abuse and Alcoholism, Rockville, Maryland 20852, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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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:
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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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