Molecular mechanism of α-tocopheryl-phosphate transport across the cell membrane

Yesim Negis, Mohsen Meydani, Jean Marc Zingg, Angelo Azzi

Research output: Contribution to journalArticlepeer-review

26 Scopus citations

Abstract

α-Tocopheryl-phosphate (α-TP) is synthesized and hydrolyzed in animal cells and tissues where it modulates several functions. α-TP is more potent than α-T in inhibiting cell proliferation, down-regulating CD36 transcription, inhibiting atherosclerotic plaque formation. Administration of α-TP to cells or animals requires its transfer through membranes, via a transporter. We show here that α-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 α-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 α-TP is transported into cells, it may be concluded that α-TP transport may occur via an OAT family member. Due to the protection by glibenclamide and probenecid on the α-TP induced cell growth inhibition it appears that α-TP acts after its uptake inside cells.

Original languageEnglish (US)
Pages (from-to)348-353
Number of pages6
JournalBiochemical and biophysical research communications
Volume359
Issue number2
DOIs
StatePublished - Jul 27 2007
Externally publishedYes

Keywords

  • α-Tocopheryl-phosphate
  • Glibenclamide
  • Organic anion transporter (OAT)
  • Probenecid
  • Tocopherol
  • Transport
  • Vitamin E

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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