{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,23]],"date-time":"2026-02-23T17:59:46Z","timestamp":1771869586176,"version":"3.50.1"},"reference-count":30,"publisher":"Proceedings of the National Academy of Sciences","issue":"23","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[1997,11,11]]},"abstract":"<jats:p>Vitamin E (\u03b1-tocopherol) is a fat-soluble antioxidant that is transported by plasma lipoproteins in the body. \u03b1-Tocopherol taken up by the liver with lipoprotein is thought to be resecreted into the plasma in very low density lipoprotein (VLDL). \u03b1-Tocopherol transfer protein (\u03b1TTP), which was recently identified as a product of the causative gene for familial isolated vitamin E deficiency, is a cytosolic liver protein and plays an important role in the efficient recycling of plasma vitamin E. To throw light on the mechanism of \u03b1TTP-mediated \u03b1-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 \u03b1-tocopherol was more efficient in cells expressing \u03b1TTP than in matched cells lacking \u03b1TTP. Brefeldin A, which effectively inhibits VLDL secretion by disrupting the Golgi apparatus, had no effect on \u03b1-tocopherol secretion, indicating that \u03b1TTP-mediated \u03b1-tocopherol secretion is not coupled to VLDL secretion. Among other agents tested, only 25-hydroxycholesterol, a modulator of cholesterol metabolism, inhibited \u03b1-tocopherol secretion. This inhibition is most likely mediated by oxysterol-binding protein. These results suggest that \u03b1TTP present in the liver cytosol functions to stimulate secretion of cellular \u03b1-tocopherol into the extracellular medium and that the reaction utilizes a novel non-Golgi-mediated pathway that may be linked to cellular cholesterol metabolism and\/or transport.<\/jats:p>","DOI":"10.1073\/pnas.94.23.12437","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T14:31:44Z","timestamp":1027693904000},"page":"12437-12441","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":105,"title":["\u03b1-Tocopherol transfer protein stimulates the secretion of \u03b1-tocopherol from a cultured liver cell line through  a brefeldin A-insensitive\u2009pathway"],"prefix":"10.1073","volume":"94","author":[{"given":"Makoto","family":"Arita","sequence":"first","affiliation":[{"name":"Department of Health Chemistry, Graduate School of Pharmaceutical Sciences, University of Tokyo, Hongo 7-3-1, 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