Blood-to-retina transport of riboflavin via RFVTs at the inner blood-retinal barrier
Blood-to-retina transport of riboflavin via RFVTs at the inner blood-retinal barrier
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DOI：
10.1016/j.dmpk.2016.09.006
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发表时间：
2017-02-01
影响因子：
2.1
通讯作者：
Hosoya, Ken-ichi
中科院分区：
文献类型：
--
作者：
Kubo, Yoshiyuki;Yahata, Shizuka;Hosoya, Ken-ichi
研究了核黄素(维生素B2)通过血-视网膜内屏障(BRB)向视网膜的供应。在大鼠中，[H-3]核黄素的表观通透性清除率(62.8u L/分钟视网膜)远高于非通透性旁细胞标志物，提示核黄素促进了核黄素跨视网膜的内流转运。黄素腺嘌呤二核苷酸(FAD)对核黄素的摄取指数(RUI)为59.0%，黄素腺嘌呤二核苷酸(FAD)对核黄素摄取指数(RUI)为59.0%，而L抗坏血酸对核黄素摄取指数RUI为59.0%，提示核黄素转运具有底物特异性。[H-3]不含Na+和Cl(-)的缓冲液对[H-3]核黄素的摄取略有改变，表明核黄素在BRB内侧的转运优先不依赖于Na+和Cl(-)。[H-3]核黄素类似物显著降低了TR-iBRB2细胞对核黄素的摄取，而其他维生素对核黄素的摄取不变。功能和抑制谱表明核黄素转运体(SLC52A/RFVT)参与了核黄素在BRB内部的转运，这一结果得到了tr-iBRB2细胞中rRFVT2(SLC52a2)和rRFVT3(SLc52a3)的表达和敲除分析的支持。(C)爱思唯尔有限公司出版的2016年。
Riboflavin (vitamin B2) supply to the retina across the inner blood-retinal barrier (BRB) was investigated. In rats, the apparent influx permeability clearance of [H-3]riboflavin (62.8 mu L/(min.g retina) was much higher than that of a non- permeable paracellular marker, suggesting the facilitative influx transport of riboflavin across the BRB. The retinal uptake index (RUI) of [H-3] riboflavin was 59.0%, and significantly reduced by flavin adenine dinucleotide (FAD), but not by L-ascorbic acid, suggesting the substrate specificity of riboflavin transport.TR-iBRB2 cells, an in vitro model of the inner BRB, showed a temperature-and concentration-dependent [H-3] riboflavin uptake with a K-m of 113 nM, suggesting that the influx transport of riboflavin across the inner BRB involves a carrier- mediated process. [H-3] Riboflavin uptake by TR-iBRB2 cells was slightly altered by Na+- and Cl (-) -free buffers, suggesting that riboflavin transport at the inner BRB is preferentially Na+- and Cl (-) -independent. [H-3] Riboflavin uptake by TR-iBRB2 cells was significantly reduced by riboflavin analogues while the uptake remained unchanged by other vitamins. The function and inhibition profile suggested the involvement of riboflavin transporters (SLC52A/RFVT) in riboflavin transport at the inner BRB, and this is supported by expression and knockdown analysis of rRFVT2 (Slc52a2) and rRFVT3(Slc52a3) in TR-iBRB2 cells. (C) 2016 Published by Elsevier Ltd.