Sulfatides are required for renal adaptation to chronic metabolic acidosis
Sulfatides are required for renal adaptation to chronic metabolic acidosis
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肾脏适应慢性代谢性酸中毒需要硫苷脂
DOI：
10.1073/pnas.1217775110
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发表时间：
2013
期刊：
影响因子：
--
通讯作者：
Jennemann R
中科院分区：
文献类型：
--
作者：
Stettner P;Bourgeois S;Marsching C;Traykova-Brauch M;Porubsky S;Nordstrom V;Hopf C;Koesters R;Sandhoff R;Wiegandt H;Wagner CA;Grone HJ;Jennemann R
肾排泄尿铵对于肾排泄足够量的质子和维持稳定的血液pH值是必不可少的。集合管上皮细胞的铵分泌占尿铵的大部分;由于髓质和乳头状肾小管中铵的积累，其由肾小管至管腔的NH3梯度驱动。在这里，我们证明了硫苷脂，高度带电的阴离子鞘糖脂，是重要的维持高乳头铵浓度和增加尿酸消除代谢性酸中毒。我们通过遗传学方法沿沿着整个肾小管破坏硫苷脂合成。肾硫脂缺乏小鼠尿pH值较低，伴随着较低的铵排泄。在酸性饮食，他们表现出受损的氨尿，减少铵积累的乳头，慢性高尿酸代谢性酸中毒。在突变小鼠中，产氨酶和Na+-K+/NH 4 +-2Cl-协同转运蛋白2的表达水平更高，并且通过皮质和外髓集合管的体外微灌注检测的跨上皮NH3转运不受影响。因此，我们认为，硫苷脂作为抗衡离子促进其保留在乳头间质铵。本研究指出硫苷脂在肾氨处理、尿酸化和酸碱平衡中的重要作用。
Urinary ammonium excretion by the kidney is essential for renal excretion of sufficient amounts of protons and to maintain stable blood pH. Ammonium secretion by the collecting duct epithelia accounts for the majority of urinary ammonium; it is driven by an interstitium-to-lumen NH3gradient due to the accumulation of ammonium in the medullary and papillary interstitium. Here, we demonstrate that sulfatides, highly charged anionic glycosphingolipids, are important for maintaining high papillary ammonium concentration and increased urinary acid elimination during metabolic acidosis. We disrupted sulfatide synthesis by a genetic approach along the entire renal tubule. Renal sulfatide-deficient mice had lower urinary pH accompanied by lower ammonium excretion. Upon acid diet, they showed impaired ammonuria, decreased ammonium accumulation in the papilla, and chronic hyperchloremic metabolic acidosis. Expression levels of ammoniagenic enzymes and Na+-K+/NH4+-2Cl−cotransporter 2 were higher, and transepithelial NH3transport, examined by in vitro microperfusion of cortical and outer medullary collecting ducts, was unaffected in mutant mice. We therefore suggest that sulfatides act as counterions for interstitial ammonium facilitating its retention in the papilla. This study points to a seminal role of sulfatides in renal ammonium handling, urinary acidification, and acid–base homeostasis.
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影响因子：
19.6
作者：
Sakhaee, Khashayar
通讯作者：
Sakhaee, Khashayar
影响因子：
8.8
作者：
Kobayashi T;Honke K;Kamio K;Sakakibara N;Gasa S;Miyao N;Tsukamoto T;Ishizuka I;Miyazaki T;Makita A
通讯作者：
Makita A
DOI：
10.1073/pnas.93.23.13280
发表时间：
1996-11-12
影响因子：
11.1
作者：
Bosio, A;Binczek, E;Stoffel, W
通讯作者：
Stoffel, W
影响因子：
64.8
作者：
Biver, Sophie;Belge, Hendrica;Marini, Anna Maria
通讯作者：
Marini, Anna Maria
哺乳动物细胞中的 NKCC2 表面表达
影响因子：
4.8
作者：
B. Benziane;Sylvie Demaretz;N. Defontaine;N. Zaarour;L. Cheval;Soline Bourgeois;C. Klein;M. Froissart;A. Blanchard;M. Paillard;G. Gamba;P. Houillier;K. Laghmani
通讯作者：
K. Laghmani