Journal
REDOX BIOLOGY
Volume 19, Issue -, Pages 28-36Publisher
ELSEVIER
DOI: 10.1016/j.redox.2018.07.027
Keywords
Endoplasmic reticulum; HepG2 liver cells; Intracellular localization; Lysosomes; Mitochondria; Plasma membrane; alpha-Tocopherol transfer protein; Tocotrienols; Trafficking; Vitamin E
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Funding
- foundation Fiat Panis
- Food Security Center of the University of Hohenheim - German Academic Exchange Service (DAAD)
- Federal Ministry of Economic Cooperation and Development (BMZ) of Germany
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Liver cells express a cytosolic alpha-tocopherol transfer protein (alpha TTP) with high binding affinity for alpha-tocopherol (alpha T) and much lower affinities for the non-alpha T congeners. The role of alpha TTP in the intracellular distribution of the different vitamin E forms is currently unknown. We therefore investigated the intracellular localization of alpha T, gamma-tocopherol (gamma T), alpha-tocotrienol (alpha T3), and gamma-tocotrienol (gamma T3) in cultured hepatic cells with and without stable expression of alpha TTP. We first determined cellular uptake of the four congeners and found the methylation of the chromanol ring and saturation of the sidechain to be important factors, with tocotrienols being taken up more efficiently than tocopherols and the gamma-congeners more than the alpha-congeners, irrespective of the expression of alpha TTP. This, however, could perhaps also be due to an observed higher stability of tocotrienols, compared to tocopherols, in culture media rather than a higher absorption. We then incubated HepG2 cells and alpha TTP-expressing HepG2 cells with alpha T, gamma T, alpha T3, or gamma T3, isolated organelle fractions by density gradient centrifugation, and determined the concentrations of the congeners in the subcellular fractions. All four congeners were primarily associated with the lysosomes, endoplasmic reticulum, and plasma membrane, whereas only alpha T correlated with mitochondria. Neither the chromanol ring methylation or sidechain saturation, nor the expression of alpha TTP were important factors for the intracellular distribution of vitamin E. In conclusion, alpha TTP does not appear to regulate the uptake and intracellular localization of different vitamin E congeners in cultured liver cells.
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