Mototada Shichiri, Yasukazu Takanezawa, Daisy E Rotzoll, Yasukazu Yoshida, Tomokuni Kokubu, Kazumitsu Ueda, Hiroshi Tamai, Hiroyuki Arai
Department of Health Chemistry, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo, Japan.
The Journal of nutritional biochemistry 2010 MayVitamin E (alpha-tocopherol) is an essential fat-soluble nutrient with antioxidant properties. alpha-Tocopherol transfer protein (alpha-TTP), the product of the gene responsible for familial isolated vitamin E deficiency, plays an important role in maintaining the plasma alpha-tocopherol level by mediating the secretion of alpha-tocopherol by the liver. However, the mechanisms underlying hepatic alpha-tocopherol secretion are not fully understood. This study was undertaken to elucidate the mechanism of alpha-tocopherol re-efflux from hepatocytes, the cells that have the most important role in regulating plasma-alpha-tocopherol concentrations. From in vitro experiments using [(3)H]alpha-tocopheryl acetate and McARH7777 cells that stably express alpha-tocopherol transfer protein (alpha-TTP), the following results were obtained. First, addition of apolipoprotein A-I (apoA-I), a direct acceptor of the ATP-binding cassette transporter A1 (ABCA1)-secreted lipids, increased alpha-tocopherol secretion in a dose-dependent manner. Second, probucol, an antiatherogenic compound reported to be an inactivator of ABCA1 reduced hepatic alpha-tocopherol secretion. Third, ABCA1-RNAi suppressed hepatic alpha-tocopherol secretion. In a mouse in vivo experiment, addition of 1% probucol to the diet decreased plasma alpha-tocopherol concentrations. These results strongly suggest that ABCA1 is substantially involved in hepatic alpha-tocopherol secretion. Copyright 2010 Elsevier Inc. All rights reserved.
Mototada Shichiri, Yasukazu Takanezawa, Daisy E Rotzoll, Yasukazu Yoshida, Tomokuni Kokubu, Kazumitsu Ueda, Hiroshi Tamai, Hiroyuki Arai. ATP-binding cassette transporter A1 is involved in hepatic alpha-tocopherol secretion. The Journal of nutritional biochemistry. 2010 May;21(5):451-6
PMID: 19427182
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