dc.contributor.author | Davis, Sterenn | |
dc.contributor.author | Davis, Benjamin M. | |
dc.contributor.author | Richens, Joanna L. | |
dc.contributor.author | Vere, Kelly-Ann | |
dc.contributor.author | Petrov, Peter G. | |
dc.contributor.author | Winlove, C. Peter | |
dc.contributor.author | O'Shea, Paul | |
dc.date.accessioned | 2016-03-08T10:02:46Z | |
dc.date.issued | 2015-08 | |
dc.description.abstract | α-Tocopherol (vitamin E) has attracted considerable attention as a potential protective or palliative agent. In vitro, its free radical-scavenging antioxidant action has been widely demonstrated. In vivo, however, vitamin E treatment exhibits negligible benefits against oxidative stress. α-Tocopherol influences lipid ordering within biological membranes and its derivatives have been suggested to inhibit the multi-drug efflux pump, P-glycoprotein (P-gp). This study employs the fluorescent membrane probe, 1-(3-sulfonatopropyl)-4-[β[2-(di-n-octylamino)-6-naphthyl]vinyl] pyridinium betaine, to investigate whether these effects are connected via influences on the membrane dipole potential (MDP), an intrinsic property of biological membranes previously demonstrated to modulate P-gp activity. α-Tocopherol and its non-free radical-scavenging succinate analog induced similar decreases in the MDP of phosphatidylcholine vesicles. α-Tocopherol succinate also reduced the MDP of T-lymphocytes, subsequently decreasing the binding affinity of saquinavir for P-gp. Additionally, α-tocopherol succinate demonstrated a preference for cholesterol-treated (membrane microdomain enriched) cells over membrane cholesterol-depleted cells. Microdomain disruption via cholesterol depletion decreased saquinavir's affinity for P-gp, potentially implicating these structures in the influence of α-tocopherol succinate on P-gp. This study provides evidence of a microdomain dipole potential-dependent mechanism by which α-tocopherol analogs influence P-gp activity. These findings have implications for the use of α-tocopherol derivatives for drug delivery across biological barriers. | en_GB |
dc.identifier.citation | Vol. 56, pp. 1543 - 1550 | en_GB |
dc.identifier.doi | 10.1194/jlr.M059519 | |
dc.identifier.other | jlr.M059519 | |
dc.identifier.uri | http://hdl.handle.net/10871/20585 | |
dc.language.iso | en | en_GB |
dc.publisher | American Society for Biochemistry and Molecular Biology | en_GB |
dc.relation.url | http://www.ncbi.nlm.nih.gov/pubmed/26026069 | en_GB |
dc.relation.url | http://www.asbmb.org/page.aspx?id=642 | en_GB |
dc.subject | antioxidants | en_GB |
dc.subject | cholesterol | en_GB |
dc.subject | lipid rafts | en_GB |
dc.subject | saquinavir | en_GB |
dc.subject | vitamin E | en_GB |
dc.title | α-Tocopherols modify the membrane dipole potential leading to modulation of ligand binding by P-glycoprotein | en_GB |
dc.type | Article | en_GB |
dc.date.available | 2016-03-08T10:02:46Z | |
dc.identifier.issn | 0022-2275 | |
exeter.place-of-publication | United States | |
dc.description | Journal Article | en_GB |
dc.description | This is the author accepted manuscript. The final version is available from ASBMB via the DOI in this record. | en_GB |
dc.identifier.journal | Journal of Lipid Research | en_GB |