COMPARISON OF RRR-ALPHA-TOCOPHEROL AND ALL-RAC-ALPHA-TOCOPHEROL UPTAKE BY PERMANENT RAT SKELETAL-MUSCLE MYOBLASTS (L6 CELLS) - EFFECTS OF EXOGENOUS LIPOPROTEIN-LIPASE

The purpose of the present investigation was to test whether permanent skeletal muscle cells (rat L6 cells) could serve as an in vitro model for alpha-tocopherol (alpha TocH) biodiscrimination studies. L6 cells were incubated in the presence of high density lipoprotein (HDL), low density lipoprotein (LDL), and very low density lipoprotein (VLDL) la beled in the lipid moiety with either all-rac- or RRR-[C-14]alpha TocH . These incubations were performed either in the absence or in the pre sence of exogenously added bovine lipoprotein lipase (LPL) since skele tal muscle is one of the major expression sites of LPL in vivo. Time-d ependent uptake studies (up to 24 h) in the absence of LPL have shown that equipotent doses of all-rac- and RRR-[C-14]alpha TocH (1.36:1) le d to almost identical accumulation of the tracer, independent of the l ipoprotein class used as alpha TocH carrier. With regard to alpha TocH donor capacity, it appeared that HDL is the most potent alpha TocH do nor, followed by LDL and VLDL. In the presence of LPL, all-rac- and RR R-[C-14]alpha TocH uptake was significantly enhanced (between two- and tenfold). Biodiscrimination studies using chiral high-performance liq uid chromatographic analysis with radiometric detection of the corresp onding methyl ether derivatives on a Chiralcel OD column have demonstr ated that the 2S- and 2R-isomers of alpha TocH were taken up in a 1:1 ratio by L6 cells independent of the absence or presence of LPL. In ad dition, we have not observed biodiscrimination between the four 2R-iso mers, i.e., there was no preferential accumulation of the RRR-isomer. These data suggest that L6 cells do not discriminate between different alpha TocH isomers and that the addition of endogenous LPL significan tly enhances the uptake of RRR- and all-rac-alpha TocH.