Effect of dietary protein restriction on renal ammonia metabolism.
Effect of dietary protein restriction on renal ammonia metabolism.
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膳食蛋白质限制对肾氨代谢的影响。
DOI：
10.1152/ajprenal.00077.2015
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发表时间：
2015
期刊：
影响因子：
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通讯作者：
Weiner,IDavid
中科院分区：
文献类型：
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作者：
Lee,Hyun-Wook;Osis,Gunars;Handlogten,MaryE;Guo,Hui;Verlander,JillW;Weiner,IDavid
饮食蛋白质限制对肾脏疾病有多重好处。由于蛋白质摄入是内源性酸产生的主要决定因素，因此在蛋白质限制期间，净酸排泄平行变化是很重要的。氨是净酸排泄的主要成分，氨排泄不当会导致氮负平衡。因此，我们检测了氨排泄对蛋白质限制的反应，然后确定了所观察到的变化的分子机制。野生型C57Bl/6小鼠先喂食20%蛋白质，然后改为6%蛋白质，在2天内氨排泄量减少85%，并在10天的研究中持续存在。参与肾氨代谢的多种蛋白的表达发生改变，包括氨生成酶磷酸依赖谷氨酰胺酶（PDG）和磷酸烯醇丙酮酸羧激酶（PEPCK）以及氨代谢酶谷氨酰胺合成酶。氨转运蛋白Rhbg在外髓集管插层细胞（OMCDis-IC）内条表达增加。然而，收集管道特异性Rhbg缺失并没有改变对蛋白质限制的反应。Rhcg的缺失没有改变氨排泄对饮食蛋白质限制的反应。综上所述，1)饲粮限制蛋白质通过协调调节氨代谢的多种组分来减少肾氨排泄；2) OMCDis-IC中Rhbg表达的增加可能表明除了氨转运外还具有生物学作用；3)饲粮限制蛋白质时，Rhcg的表达对于减少氨排泄并不是必需的。
Dietary protein restriction has multiple benefits in kidney disease. Because protein intake is a major determinant of endogenous acid production, it is important that net acid excretion change in parallel during protein restriction. Ammonia is the primary component of net acid excretion, and inappropriate ammonia excretion can lead to negative nitrogen balance. Accordingly, we examined ammonia excretion in response to protein restriction and then we determined the molecular mechanism of the changes observed. Wild-type C57Bl/6 mice fed a 20% protein diet and then changed to 6% protein developed an 85% reduction in ammonia excretion within 2 days, which persisted during a 10-day study. The expression of multiple proteins involved in renal ammonia metabolism was altered, including the ammonia-generating enzymes phosphate-dependent glutaminase (PDG) and phosphoenolpyruvate carboxykinase (PEPCK) and the ammonia-metabolizing enzyme glutamine synthetase. Rhbg, an ammonia transporter, increased in expression in the inner stripe of outer medullary collecting duct intercalated cell (OMCDis-IC). However, collecting duct-specific Rhbg deletion did not alter the response to protein restriction. Rhcg deletion did not alter ammonia excretion in response to dietary protein restriction. These results indicate1) dietary protein restriction decreases renal ammonia excretion through coordinated regulation of multiple components of ammonia metabolism;2) increased Rhbg expression in the OMCDis-IC may indicate a biological role in addition to ammonia transport; and3) Rhcg expression is not necessary to decrease ammonia excretion during dietary protein restriction.