Expression of slc5a8 in kidney and its role in Na+-coupled transport of lactate
Expression of slc5a8 in kidney and its role in Na+-coupled transport of lactate
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DOI：
10.1074/jbc.m405365200
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发表时间：
2004-10-22
影响因子：
4.8
通讯作者：
Ganapathy, V
中科院分区：
文献类型：
--
作者：
Gopal, E;Fei, YJ;Ganapathy, V
我们在这里报告slc 5a 8在肾脏中的表达及其与Na+-偶联的乳酸重吸收的相关性。slc 5a 8是SLC 5A 8的小鼠直系同源物，SLC 5A 8是一种候选肿瘤抑制基因，我们最近从人肠道中克隆了SLC 5A 8，并证明了其作为短链脂肪酸和乳酸的Na+偶联转运蛋白的功能特性。slc 5a 8 cDNA克隆自小鼠肾脏，编码由611个氨基酸组成的蛋白质。当在哺乳动物细胞或爪蟾卵母细胞中异源表达时，slc 5a 8介导乳酸/丙酮酸以及短链脂肪酸（例如，G.乙酸盐、丙酸盐和丁酸盐）。Na+/脂肪酸化学计量根据脂肪酸底物而变化（乳酸盐为2：1，丙酸盐为4：1）。这种Na+/底物化学计量可变的现象取决于脂肪酸底物，也可以用人SLC 5A 8证明。小鼠肾脏矢状面原位杂交结果显示，该基因在肾皮质和髓质均有大量表达。从兔肾制备的刷状缘膜囊泡能够以Na+偶联方式转运乳酸。转运过程中表现出超调现象，表明响应跨膜Na+梯度的上坡乳酸转运。Na+-偶联乳酸在这些膜囊泡的运输是可重复的短链脂肪酸。我们的结论是，slc 5a 8在肾脏中表达丰富，并在乳酸的主动重吸收中发挥作用。slc 5a 8是已知在哺乳动物肾脏中表达的第一种转运蛋白，其具有介导乳酸盐的Na+偶联重吸收的能力。
We report here on the expression of slc5a8 in kidney and its relevance to Na+-coupled reabsorption of lactate. slc5a8 is the murine ortholog of SLC5A8, a candidate tumor suppressor gene, which we recently cloned from human intestine and demonstrated its functional identity as a Na+-coupled transporter for short-chain fatty acids and lactate. The slc5a8 cDNA, cloned from mouse kidney, codes for a protein consisting of 611 amino acids. When expressed heterologously in mammalian cells or Xenopus oocytes, slc5a8 mediates Na+-coupled electrogenic transport of lactate/pyruvate as well as short-chain fatty acids ( e. g. acetate, propionate, and butyrate). The Na+/fatty acid stoichiometry varies depending on the fatty acid substrate ( 2: 1 for lactate and 4: 1 for propionate). This phenomenon of variable Na+/ substrate stoichiometry depending on the fatty acid substrate is also demonstrable with human SLC5A8. In situ hybridization with sagittal sections of mouse kidney demonstrates abundant expression of the transcripts in the cortex as well as the medulla. Brush border membrane vesicles prepared from rabbit kidney are able to transport lactate in a Na+-coupled manner. The transport process exhibits the overshoot phenomenon, indicating uphill lactate transport in response to the transmembrane Na+ gradient. The Na+-coupled lactate transport in these membrane vesicles is inhibitable by short-chain fatty acids. We conclude that slc5a8 is expressed abundantly in the kidney and that it plays a role in the active reabsorption of lactate. slc5a8 is the first transporter known to be expressed in mammalian kidney that has the ability to mediate the Na+-coupled reabsorption of lactate.