Chronic metabolic acidosis increases NHE3 protein abundance in rat kidney
Chronic metabolic acidosis increases NHE3 protein abundance in rat kidney
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DOI：
10.1152/ajprenal.1996.271.4.f917
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发表时间：
1996-10-01
期刊：
影响因子：
--
通讯作者：
Alpern, RJ
中科院分区：
文献类型：
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作者：
Ambuhl, PM;Amemiya, M;Alpern, RJ
慢性代谢性酸中毒增加了近曲小管顶膜Na/H逆向转运蛋白的活性，该转运蛋白主要由NHE3亚型编码。本研究探讨了慢性代谢性酸中毒对大鼠根尖膜NHE3蛋白丰度的影响。在饮用水中加入NH4Cl的大鼠出现代谢性酸中毒，其程度在14天内下降。在此期间，用免疫印迹法检测肾皮质刷状缘膜NHE3蛋白丰度，逐渐增加(3天28%，7天59%，14天90%)。免疫组织化学结果显示，酸中毒引起的NHE3丰度增加发生在近端小管的S1、S2段和粗大的升肢的顶膜。NHE3mRNA丰度在这些动物中没有显著增加，而磷酸烯醇式丙酮酸羧激酶和甘油醛-3-磷酸脱氢酶mRNA丰度显著增加。这些研究表明，代谢性酸中毒中Na/H逆向转运蛋白活性的增加与NHE3蛋白丰度的增加有关，NHE3蛋白沿近端小管和粗大的升肢分布。此外，这些研究表明，这种适应的一个组成部分与NHE3 mRNA丰度的变化无关。
Chronic metabolic acidosis increases the activity of the proximal tubule apical membrane Na/H antiporter, which is encoded predominantly by the NHE3 isoform. The present studies examined the effect of chronic metabolic acidosis on apical membrane NHE3 protein abundance in rats. Rats subjected to NH4Cl in their drinking water developed a metabolic acidosis, which decreased in magnitude over 14 days. During this time, renal cortical brush-border membrane NHE3 protein abundance, assessed by Western blot, increased progressively (28% at 3 days, 59% at 7 days, and 90% at 14 days). Immunohistochemistry revealed that the acidosis-induced increase in NHE3 abundance occurred in the apical membranes of the S1 and S2 segments of the proximal tubule and the thick ascending limb. NHE3 mRNA abundance was not significantly increased in these animals, whereas phosphoenolpyruvate carboxykinase and glyceraldehyde-3-phosphate dehydrogenase mRNA abundances were significantly increased. These studies demonstrate that the increase in Na/H antiporter activity seen in metabolic acidosis involves an increase in NHE3 protein abundance, which is distributed along the proximal tubule and the thick ascending limb. In addition, these studies suggest that a component of this adaptation is unrelated to changes in NHE3 mRNA abundance.