The natural vitamin E analog alpha-tocopheryl phosphate (alphaTP) modulates atherosclerotic and inflammatory events more efficiently than the unphosphorylated alpha-tocopherol (alphaT). To investigate the molecular mechanisms involved, we have measured plasma levels of alphaTP and compared the cellular effects of alphaT and alphaTP in THP-1 monocytes. THP-1 cell proliferation is slightly increased by alphaT, whereas it is inhibited by alphaTP. CD36 surface expression is inhibited by alphaTP within hours without requiring transport of alphaTP into cells, suggesting that alphaTP may bind to CD36 and/or trigger its internalization. As assessed by gene expression microarrays, more genes are regulated by alphaTP than by alphaT. Among a set of confirmed genes, the expression of vascular endothelial growth factor is induced by alphaTP as a result of activating protein kinase B (PKB/Akt) and is associated with increased levels of reactive oxygen species (ROS). Increased Akt(Ser473) phosphorylation and induction of ROS by alphaTP occur in a wortmannin-sensitive manner, indicating the involvement of phosphatidylinositol kinases. The induction of Akt(Ser473) phosphorylation and ROS production by alphaTP can be attenuated by alphaT. It is concluded that alphaTP and alphaT influence cell proliferation, ROS production, and Akt(Ser473) phosphorylation in an antagonistic manner, most probably by modulating phosphatidylinositol kinases.
|Pages (from-to)||1989 - 2000|
|Number of pages||12|
|Journal||Free Radical Biology and Medicine|
|Publication status||Published - 2010|