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Title: Molecular mechanism of {alpha}-tocopheryl-phosphate transport across the cell membrane

Journal Article · · Biochemical and Biophysical Research Communications
 [1];  [1];  [1];  [1]
  1. Vascular Biology Laboratory, The Jean Mayer USDA Human Nutrition Center at Tufts University, 711 Washington Street, Boston, MA 02111 (United States)

{alpha}-Tocopheryl-phosphate ({alpha}-TP) is synthesized and hydrolyzed in animal cells and tissues where it modulates several functions. {alpha}-TP is more potent than {alpha}-T in inhibiting cell proliferation, down-regulating CD36 transcription, inhibiting atherosclerotic plaque formation. Administration of {alpha}-TP to cells or animals requires its transfer through membranes, via a transporter. We show here that {alpha}-TP is passing the plasma membrane via a system that is inhibited by glibenclamide and probenecid, inhibitors of a number of transporters. Glibenclamide and probenecid prevent dose-dependently {alpha}-TP inhibition of cell proliferation. The two inhibitors act on ATP binding cassette (ABC) and organic anion transporters (OAT). Since ABC transporters function to export solutes and {alpha}-TP is transported into cells, it may be concluded that {alpha}-TP transport may occur via an OAT family member. Due to the protection by glibenclamide and probenecid on the {alpha}-TP induced cell growth inhibition it appears that {alpha}-TP acts after its uptake inside cells.

OSTI ID:
20991458
Journal Information:
Biochemical and Biophysical Research Communications, Vol. 359, Issue 2; Other Information: DOI: 10.1016/j.bbrc.2007.05.094; PII: S0006-291X(07)01061-3; Copyright (c) 2007 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); ISSN 0006-291X
Country of Publication:
United States
Language:
English

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