ビタミンE輸送タンパク質を介する肝細胞内ビタミンE輸送機構

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Vitamin E (E, α-tocopherol) is a fat-soluble antioxidant that is transported by plasma lipoproteins in the body. α-Tocopherol taken up by the liver with lipoprotein is thought to be re-secreted into the plasma in very low density lipoprotein(VLDL). α-Tocopherol transfer protein ( αTTP), which was recently identified as a product of the causative gene for familial isolated E deficiency, is a cytosolic liver protein and plays an important role in the efficient recycling of plasma E. To throw light on the mechanism of αTTP-mediated α-tocopherol transfer in the liver cell, we devised an assay system using the hepatoma cell line McARH7777. Using this system, we found that the secretion of α-tocopherol was more efficient in cells expressing αTTP than in matched cells lacking αTTP. Brefeldin A, which effectively inhibits VLDL secretion by disrupting the Golgi apparatus, had no effect on α-tocopherol secrertion, indicating that αTTP-mediated α-tocopherol secretion is not coupled to VLDL secretion. Among other agents tested, only 25-hydroxycholesterol, a modulator of cholesterol metabolism, inhibited α-tocopherol secretion. This inhibition is most likely mediated by oxysterol binding protein. These results suggest that αTTP present in the liver cytosol functions to stimulate secretion of cellular α-tocopherol into the extracellular medium and that tha reaciton utilizes a novel non-Golgi mediated pathway which may be linked to cellular cholesterol metabolism and/or transport.
日本ビタミン学会の論文
1998-08-25

ビタミンE輸送タンパク質を介する肝細胞内ビタミンE輸送機構

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