We previously reported that tocotrienols acted as more potent inhibitors against selenium deficiency-induced cell death than the corresponding tocopherol isoforms (J. Biol. Chem. 2003;278:39428-39434). In the present study, we first compared the differences in the cellular uptake between α-tocopherol (α-Toc) and α-tocotrienol (α-Toc-3). The initial rate of cellular uptake of α-Toc-3 was 70-fold higher than that of α-Toc. Subcellular fractionation analysis of α-Toc-3 and α-Toc-fortified cells showed similar cellular distribution of these antioxidants, which was directly proportional to the lipid distribution. The cells containing similar amounts of α-Toc-3 and α-Toc showed similar resistance against the oxidative stress caused by peroxides. These results suggest that the apparent higher cytoprotective effect of α-Toc-3 than α-Toc is primarily ascribed to its higher cellular uptake.
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