ATP-Binding cassette transporter A1 is involved in hepatic alpha-tocopherol secretion

作者：Shichiri Mototada; Takanezawa Yasukazu; Rotzoll Daisy E; Yoshida Yasukazu; Kokubu Tomokuni; Ueda Kazumitsu; Tamai Hiroshi; Arai Hiroyuki^*

来源：Journal of Nutritional Biochemistry, 2010, 21(5): 451-456.

DOI：10.1016/j.jnutbio.2009.02.002

• alpha-Tocopherol
• ATP-Binding cassette transporter A1 (ABCA1)
• alpha-Tocopherol transfer protein (alpha-TTP)
• Hepatocyte
• Apolipoprotein A-I (apoA-I)
• Probucol

Vitamin E (alpha-tocopherol) is an essential fat-soluble nutrient with antioxidant properties, alpha-Tocopherol transfer protein (alpha-UP), 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 a-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 a-tocopherol transfer protein (alpha-UP), 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.

• 出版日期2010-5