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首页> 外文期刊>Journal of Neurochemistry: Offical Journal of the International Society for Neurochemistry >Major involvement of Na+-dependent multivitamin transporter (SLC5A6/SMVT) in uptake of biotin and pantothenic acid by human brain capillary endothelial cells
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Major involvement of Na+-dependent multivitamin transporter (SLC5A6/SMVT) in uptake of biotin and pantothenic acid by human brain capillary endothelial cells

机译：Na +依赖的多种维生素转运蛋白（SLC5A6 / SMVT）主要参与人脑毛细血管内皮细胞摄取生物素和泛酸

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摘要

The purpose of this study was to clarify the expression of Na+-dependent multivitamin transporter (SLC5A6/SMVT) and its contribution to the supply of biotin and pantothenic acid to the human brain via the blood-brain barrier. DNA microarray and immunohistochemical analyses confirmed that SLC5A6 is expressed in microvessels of human brain. The absolute expression levels of SLC5A6 protein in isolated human and monkey brain microvessels were 1.19 and 0.597fmol/g protein, respectively, as determined by a quantitative targeted absolute proteomics technique. Using an antibody-free method established by Kubo etal. (2015), we found that SLC5A6 was preferentially localized at the luminal membrane of brain capillary endothelium. Knock-down analysis using SLC5A6 siRNA showed that SLC5A6 accounts for 88.7% and 98.6% of total [H-3]biotin and [H-3]pantothenic acid uptakes, respectively, by human cerebral microvascular endothelial cell line hCMEC/D3. SLC5A6-mediated transport in hCMEC/D3 was markedly inhibited not only by biotin and pantothenic acid, but also by prostaglandin E2, lipoic acid, docosahexaenoic acid, indomethacin, ketoprofen, diclofenac, ibuprofen, phenylbutazone, and flurbiprofen. This study is the first to confirm expression of SLC5A6 in human brain microvessels and to provide evidence that SLC5A6 is a major contributor to luminal uptake of biotin and pantothenic acid at the human blood-brain barrier.
机译：本研究的目的是阐明Na +依赖的多种维生素转运蛋白（SLC5A6 / SMVT）的表达及其对通过血脑屏障向人脑供应生物素和泛酸的贡献。 DNA微阵列和免疫组织化学分析证实SLC5A6在人脑的微血管中表达。通过定量靶向绝对蛋白质组学技术测定，在分离的人和猴脑微血管中SLC5A6蛋白的绝对表达水平分别为1.19和0.597fmol / g蛋白。使用Kubo等人建立的无抗体方法。 （2015），我们发现SLC5A6优先定位在脑毛细血管内皮腔膜。使用SLC5A6 siRNA进行的基因敲除分析表明，SLC5A6分别占人脑微血管内皮细胞hCMEC / D3吸收[H-3]生物素和[H-3]泛酸总量的88.7％和98.6％。 SCM5 / 6介导的hCMEC / D3中的转运不仅被生物素和泛酸显着抑制，还被前列腺素E2，硫辛酸，二十二碳六烯酸，吲哚美辛，酮洛芬，双氯芬酸，布洛芬，苯基丁but和氟比洛芬显着抑制。这项研究是首次证实SLC5A6在人脑微血管中的表达，并提供证据表明SLC5A6是人体血脑屏障中腔内吸收生物素和泛酸的主要因素。

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