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ARS Home » Northeast Area » Boston, Massachusetts » Jean Mayer Human Nutrition Research Center On Aging » Research » Publications at this Location » Publication #208787

Title: Mechanism of alpha-tocopheryl-phosphate (alpha-TP) transport across the cell membrane

Author
item NEGIS, YESIM - TUFTS/HNRCA
item Meydani, Mohsen
item AZZI, ANGELO - TUFTS/HNRCA

Submitted to: Experimental Biology
Publication Type: Abstract Only
Publication Acceptance Date: 2/6/2007
Publication Date: 4/3/2007
Citation: Negis, Y., Meydani, M., Azzi, A. 2007. Mechanism of alpha-tocopheryl-phosphate (alpha-TP) transport across the cell membrane. Experimental Biology/The FASEB Journal. 21(6):p. A1112.

Interpretive Summary:

Technical Abstract: We have reported that alpha-TP is synthesized and hydrolyzed in animal cells and tissues; it modulates also several cell functions (FRBM 39:970, and UBMB Life, 57:23, 2005). While it is similar to alpha-tocopherol (alpha-T), alpha-TP appears to be more potent than alpha-T in inhibiting cell proliferation, down regulating CD36 transcription, inhibiting atherosclerotic plaque formation etc. In cells and animals alpha-TP does not act by liberating alpha-T; rather, the intact molecule appears to be more potent than alpha-T itself (BBRC, 318:311, 2004; ABB, 450:63, 2006). Administration of alpha-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 alpha-TP on the proliferation of THP-1 was used as an indication of alpha-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 alpha-TP inhibition of cell proliferation. The data indicate that alpha-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 alpha-TP is imported, alpha-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).