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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Shaikh, Saame Raza Rockett, Benjamin Drew Salameh, Muhammad Carraway, Kristen |
| Description | Country affiliation: United States Author Affiliation: Shaikh SR ( Department of Biochemistry and Molecular Biology, Brody School of Medicine, East Carolina University, Greenville, NC 27834, USA. shaikhsa@ecu.edu) |
| Abstract | An emerging molecular mechanism by which docosahexaenoic acid (DHA) exerts its effects is modification of lipid raft organization. The biophysical model, based on studies with liposomes, shows that DHA avoids lipid rafts because of steric incompatibility between DHA and cholesterol. The model predicts that DHA does not directly modify rafts; rather, it incorporates into nonrafts to modify the lateral organization and/or conformation of membrane proteins, such as the major histocompatibility complex (MHC) class I. Here, we tested predictions of the model at a cellular level by incorporating oleic acid, eicosapentaenoic acid (EPA), and DHA, compared with a bovine serum albumin (BSA) control, into the membranes of EL4 cells. Quantitative microscopy showed that DHA, but not EPA, treatment, relative to the BSA control diminished lipid raft clustering and increased their size. Approximately 30% of DHA was incorporated directly into rafts without changing the distribution of cholesterol between rafts and nonrafts. Quantification of fluorescence colocalization images showed that DHA selectively altered MHC class I lateral organization by increasing the fraction of the nonraft protein into rafts compared with BSA. Both DHA and EPA treatments increased antibody binding to MHC class I compared with BSA. Antibody titration showed that DHA and EPA did not change MHC I conformation but increased total surface levels relative to BSA. Taken together, our findings are not in agreement with the biophysical model. Therefore, we propose a model that reconciles contradictory viewpoints from biophysical and cellular studies to explain how DHA modifies lipid rafts on several length scales. Our study supports the notion that rafts are an important target of DHA's mode of action. |
| File Format | HTM / HTML |
| ISSN | 00223166 |
| Issue Number | 9 |
| Volume Number | 139 |
| e-ISSN | 15416100 |
| Journal | Journal of Nutrition |
| Language | English |
| Publisher | American Society for Nutrition |
| Publisher Date | 2009-09-01 |
| Publisher Place | United States |
| Access Restriction | One Nation One Subscription (ONOS) |
| Subject Keyword | Membrane Microdomains Cell Membrane Oleic Acid Sucrose Antibodies Journal Article Eicosapentaenoic Acid Lipid Bilayers Cattle Physiology Cell Line Major Histocompatibility Complex Pharmacology Metabolism Drug Effects Cholesterol Docosahexaenoic Acids Membrane Proteins Chemistry B-lymphocytes Animals Models, Biological Serum Albumin, Bovine Analysis Protein Conformation Mice Discipline Nutrition |
| Content Type | Text |
| Resource Type | Article |
| Subject | Nutrition and Dietetics Medicine |
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