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Mechanism of α‐tocopheryl‐phosphate (α‐TP) transport across the cell membrane
Author(s) -
Negis Yesim,
Meydani Mosen,
Azzi Angelo
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.a1112
Subject(s) - chemistry , probenecid , transporter , multidrug resistance associated protein 2 , cell growth , cell , atp binding cassette transporter , cytotoxicity , biochemistry , membrane transport , intracellular , microbiology and biotechnology , membrane , pharmacology , in vitro , biology , gene
We have reported that α‐TP is synthesized and hydrolyzed in animal cells and tissues; it modulates also several cell functions (FRBM 39:, and UBMB Life, 57:, 2005). While it is similar to α‐tocopherol (α‐T), α‐TP appears to be more potent than α‐T in inhibiting cell proliferation, down regulating CD36 transcription, inhibiting atherosclerotic plaque formation etc. In cells and animals α‐TP does not act by liberating α‐T; rather, the intact molecule appears to be more potent than α‐T itself (BBRC, 318:, 2004; ABB, 450:, 2006). Administration of α‐TP to cells or to animals requires its transfer through membranes, an event that cannot occur by simple diffusion due to the size and the charge of the molecule but requires a transporter. The inhibitory effect of α‐TP on the proliferation of THP‐1 was used as an indication of α‐TP transport through the cell membrane. Specific transport inhibitors, glybenclamide (glyburide) and probenecid showed no inhibition of cell proliferation or cytotoxicity. However, both compounds prevented, dose‐dependently α‐TP inhibition of cell proliferation. The data indicate that α‐TP enters cells via a glybenclamide (glyburide)‐ and probenecid‐sensitive transport system. Both, members of the ABC transporter family and of the organic anion transporters (OAT), appear to be sensitive to these two inhibitors. However, since ABC transporters function to export cell solutes and α‐TP is imported, α‐TP transport may occur via an OAT family member (supported by USDA agreement No. 58‐1950‐9‐001 and Novartis and Phosphagenics fellowships to YN).