Vitamin C transporter SVCT1 serves a physiological role as a urate importer: functional analyses and in vivo investigations.
Vitamin C transporter SVCT1 serves a physiological role as a urate importer: functional analyses and in vivo investigations.
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维生素C转运蛋白SVCT1作为尿道进口商发挥了生理作用：功能分析和体内研究。
DOI：
10.1007/s00424-023-02792-1
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发表时间：
2023-04
影响因子：
4.5
通讯作者：
Takada, Tappei
中科院分区：
文献类型：
--
作者：
Toyoda, Yu;Miyata, Hiroshi;Uchida, Naohiro;Morimoto, Keito;Shigesawa, Ryuichiro;Kassai, Hidetoshi;Nakao, Kazuki;Tomioka, Naoko H.;Matsuo, Hirotaka;Ichida, Kimiyoshi;Hosoyamada, Makoto;Aiba, Atsu;Suzuki, Hiroshi;Takada, Tappei
尿酸是人体嘌呤代谢的终产物，由于其抗氧化活性以及与高尿酸血症和痛风的因果关系而至关重要。几种生理上重要的尿酸盐转运蛋白调节人体内的这种水溶性代谢物;然而，文献中已经提出存在潜在转运蛋白。我们专注于大肠杆菌尿酸盐转运蛋白YgfU，一个核碱基抗坏血酸转运蛋白（NAT）家族成员，以解决这个问题。只有SLC 23 A蛋白是人类NAT家族的成员。基于氨基酸序列与YgfU的相似性，我们假设SLC 23 A1，也称为钠依赖性维生素C转运蛋白1（SVCT 1），可能是一种尿酸盐转运蛋白。首先，我们确定了人SVCT 1和小鼠Svct 1作为钠依赖性低亲和力/高容量尿酸盐转运蛋白，使用哺乳动物细胞为基础的运输试验。接下来，使用CRISPR-Cas9系统，然后进行小鼠杂交，我们产生了缺乏尿酸盐转运蛋白1和尿酸酶的Svct 1敲除小鼠。在高尿酸血症小鼠模型中，血清尿酸水平低于对照组，表明Svct 1破坏可降低血清尿酸。考虑到Svct 1在生理学上起着肾脏维生素C再吸收剂的作用，它也可能参与尿液中尿酸盐的再吸收，尽管还需要进一步的研究来深入了解潜在的机制。我们关于SVCT 1的双底物特异性的研究结果扩展了对NAT家族蛋白中尿酸盐处理系统和功能进化变化的理解。在线版本包含补充材料，可通过10.1007/s 00424 -023-02792-1获得。
Uric acid, the end product of purine metabolism in humans, is crucial because of its anti-oxidant activity and a causal relationship with hyperuricemia and gout. Several physiologically important urate transporters regulate this water-soluble metabolite in the human body; however, the existence of latent transporters has been suggested in the literature. We focused on the Escherichia coli urate transporter YgfU, a nucleobase-ascorbate transporter (NAT) family member, to address this issue. Only SLC23A proteins are members of the NAT family in humans. Based on the amino acid sequence similarity to YgfU, we hypothesized that SLC23A1, also known as sodium-dependent vitamin C transporter 1 (SVCT1), might be a urate transporter. First, we identified human SVCT1 and mouse Svct1 as sodium-dependent low-affinity/high-capacity urate transporters using mammalian cell-based transport assays. Next, using the CRISPR-Cas9 system followed by the crossing of mice, we generated Svct1 knockout mice lacking both urate transporter 1 and uricase. In the hyperuricemic mice model, serum urate levels were lower than controls, suggesting that Svct1 disruption could reduce serum urate. Given that Svct1 physiologically functions as a renal vitamin C re-absorber, it could also be involved in urate re-uptake from urine, though additional studies are required to obtain deeper insights into the underlying mechanisms. Our findings regarding the dual-substrate specificity of SVCT1 expand the understanding of urate handling systems and functional evolutionary changes in NAT family proteins. The online version contains supplementary material available at 10.1007/s00424-023-02792-1.
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影响因子：
19.6
作者：
Castro, Tamara;Low, Marcela;Nualart, Francisco
通讯作者：
Nualart, Francisco
影响因子：
16.6
作者：
通讯作者：
--
影响因子：
1.3
作者：
Hosoyamada, Makoto;Tsurumi, Yu;Uchida, Shunya
通讯作者：
Uchida, Shunya
影响因子：
64.8
作者：
Enomoto, A;Kimura, H;Endou, H
通讯作者：
Endou, H
DOI：
10.1073/pnas.78.11.6858
发表时间：
1981-01-01
期刊：
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES
影响因子：
--
作者：
AMES, BN;CATHCART, R;HOCHSTEIN, P
通讯作者：
HOCHSTEIN, P