Involvement of riboflavin transporter RFVT2/Slc52a2 in hepatic homeostasis of riboflavin in mice
Involvement of riboflavin transporter RFVT2/Slc52a2 in hepatic homeostasis of riboflavin in mice
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核黄素转运蛋白 RFVT2/Slc52a2 参与小鼠肝脏核黄素稳态
DOI：
10.1016/j.ejphar.2013.07.042
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发表时间：
2013
期刊：
影响因子：
5
通讯作者：
Matsubara K
中科院分区：
文献类型：
--
作者：
Yao Y;Yonezawa A;Yoshimatsu H;Omura T;Masuda S;Matsubara K
核黄素（维生素B2）在肝脏中的各种生化氧化还原反应中起中介作用。肝脏核黄素稳态被认为是通过其转运蛋白来维持的。核黄素转运蛋白RFVT 2/Slc 52 a2和RFVT 3/Slc 52 a3已在啮齿类动物中鉴定。然而，每个RFVT在核黄素的肝脏稳态中的作用尚未完全阐明。在这项研究中，我们使用体外和体内研究评估了每种RFVT对肝脏摄取核黄素的贡献。小鼠原代肝细胞对核黄素的摄取呈时间和浓度依赖性增加。核黄素转运不依赖于细胞外Na+。但随着胞外pH值的升高，其摄取量沿着略有下降。Real-time PCR分析显示，Slc 52 a2（编码小鼠（m）RFVT 2）在小鼠肝脏中的mRNA水平比Slc 52 a3（编码mRFVT 3）高10倍。在pH7.4时，转染Slc 52 a2-siRNA显著降低了原代肝细胞对核黄素的摄取，而转染Slc 52 a3-siRNA则没有。此外，我们还证实了核黄素转运蛋白在体内的作用。核黄素缺乏饮食喂养8周的小鼠血浆中的核黄素浓度显著降低，但肝脏中的核黄素浓度没有显著降低。核黄素剥夺显著上调Slc 52 a2 mRNA的表达。这些结果强烈表明，mRFVT 2参与肝脏核黄素稳态。
Riboflavin (vitamin B2) acts as an intermediary during various biochemical oxidation–reduction reactions in the liver. Hepatic riboflavin homeostasis is suggested to be maintained through its transporter(s). Riboflavin transporters, RFVT2/Slc52a2and RFVT3/Slc52a3, have been identified in rodents. However, the role of each RFVT in the hepatic homeostasis of riboflavin has not yet been fully clarified. In this study, we assessed the contribution of each RFVT to riboflavin uptake into the liver usingin vitroandin vivostudies. The uptake of riboflavin by mouse primary hepatocytes increased in a time-dependent and a concentration-dependent manner. Riboflavin transport was independent of extracellular Na+. However, the uptake decreased slightly along with the extracellular pH increases. Real-time PCR analysis revealed that the mRNA level ofSlc52a2, or coding for mouse (m)RFVT2, in the mouse liver was 10 times higher than that ofSlc52a3(coding for mRFVT3). The uptake of riboflavin at pH 7.4 by primary hepatocytes was significantly decreased by the transfection ofSlc52a2-small interfering RNA (siRNA), but notSlc52a3-siRNA. Furthermore, we also confirmed the contribution of riboflavin transportersin vivo. The riboflavin concentrations in plasma, but not in the liver, were significantly decreased in mice fed on a riboflavin-deficient diet for 8 weeks. The expression ofSlc52a2mRNA was significantly upregulated by riboflavin deprivation. These results strongly suggest that mRFVT2 was involved in hepatic riboflavin homeostasis.