Renal tubular reabsorption of folate mediated by folate binding protein 1
Renal tubular reabsorption of folate mediated by folate binding protein 1
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DOI：
10.1681/asn.2004080711
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发表时间：
2005-03-01
影响因子：
13.6
通讯作者：
Finnell, RH
中科院分区：
文献类型：
--
作者：
Birn, H;Spiegelstein, O;Finnell, RH
肾小管对滤过的叶酸的重吸收对于这种重要维生素的保存和正常体内平衡至关重要。不同的分子机制涉及上皮叶酸转运，包括叶酸受体。这些缺陷表达或抗体失活与胚胎缺陷相关，也与低叶酸摄入相关;然而，它们对肾小管叶酸重吸收的贡献尚未确定。使用叶酸结合蛋白1（folbp 1）和叶酸结合蛋白2（folbp 2）基因在小鼠中的靶向失活，叶酸受体在肾上皮叶酸重吸收的作用进行了评估，在低和正常叶酸摄入。folbp 1的失活与（1）3 H-叶酸与粗肾膜结合的丧失，（2）肾叶酸清除率的增加，和（3）注射的3 H-甲基四氢叶酸的尿排泄增加和肾摄取减少有关。未观察到folbp 2失活导致肾脏叶酸处理发生变化。因此，folbp 1对于正常的肾小管叶酸重吸收是必不可少的，可以防止尿中过多的叶酸流失。Folbp 1在脉络丛、卵黄囊和胎盘中大量表达，支持Folbp 1在其他组织中叶酸转运中的作用。在低叶酸摄入条件下观察到folbp 1对肾脏叶酸摄取的最大意义，这为叶酸补充剂预防与folbp 1失活相关的发育缺陷的能力提供了可能的解释。
Renal tubular reabsorption of filtered folate is essential for the conservation and normal homeostasis of this important vitamin. Different molecular mechanisms have been implicated in epithelial folate transport, including folate receptors. Defective expression or antibody inactivation of these is associated with embryonic defects also correlated with low folate intake; however, their contribution to renal tubular folate reabsorption has not been established. With the use of targeted inactivation of the folate binding protein 1 (folbp1) and folate binding protein 2 (folbp2) genes in mice, the role of folate receptors in renal epithelial folate reabsorption was evaluated during low and normal folate intake. Inactivation of folbp1 was associated with (1) loss Of 3 H-folic acid binding to crude kidney membranes, (2) increase in renal folate clearance, and (3) increase in urinary excretion and decrease in renal uptake of injected 3 H-methyltetrahydrofolate. No changes in renal folate handling were observed as a result of folbp2 inactivation. Thus, folbp1 is essential for normal renal tubular folate reabsorption, preventing excessive urinary folate loss. Folbp1 is heavily expressed in choroid plexus, yolk sac, and placenta, supporting a role of folbp1 in folate transport in other tissues. The greatest significance of folbp1 for renal folate uptake was observed at conditions of low folate intake, providing a possible explanation for the ability of folate supplementation to prevent developmental defects associated with folbp1 inactivation.