Functional Characteristics of the Human Ortholog of Riboflavin Transporter 2 and Riboflavin-Responsive Expression of Its Rat Ortholog in the Small Intestine Indicate Its Involvement in Riboflavin Absorption

Functional Characteristics of the Human Ortholog of Riboflavin Transporter 2 and Riboflavin-Responsive Expression of Its Rat Ortholog in the Small Intestine Indicate Its Involvement in Riboflavin Absorption
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DOI:
10.3945/jn.110.128330
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发表时间:
2010-10-01
影响因子:
4.2
通讯作者:
Yuasa, Hiroaki
Yuasa, Hiroaki
中科院分区:
医学2区
文献类型:
--
作者:
Fujimura, Misaki;Yamamoto, Syunsuke;Yuasa, Hiroaki

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核黄素转运体(RFT)2最近被认为是一种转运体,主要基于其大鼠同源基因(RRFT2)的功能特征,可能参与核黄素的肠道吸收。本研究旨在进一步研究RFT2的可能作用,重点研究其人类同源基因(HRFT2)的功能特征,以及rRFT2在小肠中表达对缺乏饮食核黄素的反应。当hRFT2在人胚胎肾293细胞中瞬时表达时,能够以一种对pH敏感的方式有效地转运核黄素,有利于酸性pH,并且不需要Na+。在pH为6.0时,rRFT2对核黄素的转运是饱和的,米氏常数为0.77mU/L,并被一些核黄素衍生物如光黄素所抑制。它也被一些阳离子化合物抑制,程度较小,如乙锭。因此,hRFT2被认为具有肠道RFT的特征,同时发现它的mRNA在小肠中高表达。此外,喂养缺乏核黄素的饲料引起大鼠小肠rRFT2 mRNA表达上调,这可能是一种增强核黄素吸收的适应性反应,这可能涉及rRFT2,通过观察标记了绿色荧光蛋白的rRFT2的顶端定位特征,该rRFT2在极化的Madin-Darby犬肾脏II细胞中稳定表达。所有这些结果综合起来表明,RFT2是一种转运蛋白,参与了上皮细胞对核黄素的吸收:在小肠中的营养利用。J.Nutr.140:1722-1727,2010。
Riboflavin transporter (RFT) 2 has recently been identified as a transporter that may be, mainly based on the functional characteristics of its rat ortholog (rRFT2), involved in the intestinal absorption of riboflavin. The present study was conducted to further examine such:a possible role of RFT2, focusing on the functional characteristics of its human ortholog (hRFT2) and the response of rRFT2 expression in the small intestine to deprivation of dietary riboflavin. When transiently expressed in human embryonic kidney 293 cells, hRFT2 could transport riboflavin efficiently in a pH-sensitive manner, favoring acidic pH and without requiring Na+. Riboflavin transport by hRFT2 was saturable with a Michaelis constant of 0.77 mu mol/L at pH 6.0, and inhibited by some riboflavin derivatives, such as lumiflavin. It was also inhibited, to a lesser extent, by some cationic compounds, such as ethidium. Thus, hRFT2 was suggested to, together with a finding that its mRNA is highly expressed in the small intestine, have characteristics as an intestinal RFT. Furthermore, feeding rats a riboflavin-deficient diet caused an upregulation of the expression of rRFT2 mRNA in the small intestine, presumably as an adaptive response to enhance riboflavin absorption, Which would involve rRFT2, and its apically localized characteristic was suggested by the observation of rRFT2 tagged with green fluorescent protein stably expressed in polarized Madin-Darby canine kidney II cells. All these results combined indicate that RFT2 is a transporter involved in the epithelial uptake of riboflavin :in the small intestine for its nutritional utilization. J. Nutr. 140: 1722-1727, 2010.