Renal NHE expression and activity in neonatal NHE3-and NHE8-null mice
Renal NHE expression and activity in neonatal NHE3-and NHE8-null mice
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DOI：
10.1152/ajprenal.00492.2014
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发表时间：
2015-01-01
影响因子：
4.2
通讯作者：
Baum, Michel
中科院分区：
文献类型：
--
作者：
Pirojsakul, Kwanchai;Gattineni, Jyothsna;Baum, Michel
Na+/H+交换器(NHE)3是成年动物近端小管刷状缘膜上的主要NHE。NHE8定位于近端小管的刷状缘膜，在新生儿中的表达高于成年动物。然而，NHE8在新生儿肾酸化中的相对作用尚不清楚。本研究检测了NHE8基因缺失的新生小鼠的NHE3是否有代偿性增加，以及NHE3基因缺失的新生小鼠是否有NHE8的代偿性增加。此外，我们还检测了野生型、NHE3缺失型和NHE8缺失型小鼠对代谢性酸中毒的反应是否增加了NHE活性。我们发现，在基线时，与新生儿对照组和NHE8基因缺失小鼠相比，肾脏NHE3mRNA、总蛋白和刷状缘膜蛋白丰度相当。NHE3缺失组和对照组小鼠肾脏NHE8mRNA、总蛋白和刷状缘膜蛋白丰度相当。NHE3基因缺失和NHE8基因缺失的小鼠的NHE活动率与对照小鼠相当，但较低。接下来，我们对野生型、NHE3缺失和NHE8缺失的小鼠施加代谢性酸中毒。与赋形剂治疗的小鼠相比，酸中毒NHE8基因缺失的小鼠刷状缘膜囊泡NHE3蛋白丰度和NHE活性增加。同样，NHE3基因缺失的小鼠对代谢性酸中毒的反应是NHE8刷状缘膜蛋白丰度和NHE活性增加。综上所述，NHE3和NHE8可能在新生儿酸化中起作用。
Na+/H+ exchanger (NHE) 3 is the predominant NHE on the brush-border membrane of the proximal tubule in adult animals. NHE8 has been localized to the brush-border membrane of proximal tubules and is more highly expressed in neonates than in adult animals. However, the relative role of NHE8 in neonatal renal acidification is unclear. The present study examined if there was a compensatory increase in NHE3 in NHE8-null neonatal mice and whether there was a compensatory increase in NHE8 in NHE3-null neonatal mice. In addition, we examined whether wild-type, NHE3-null, and NHE8-null mice had an increase in NHE activity in response to metabolic acidosis. We found that at baseline, there was comparable renal NHE3 mRNA, total protein, and brush-border membrane protein abundance as in neonatal control and NHE8-null mice. There was comparable renal NHE8 mRNA, total protein, and brush-border membrane protein abundance in NHE3-null neonatal and control mice. Both NHE3-and NHE8-null mice had a comparable but lower rate of NHE activity than control mice. We next imposed metabolic acidosis in wild-type, NHE3-null, and NHE8-null mice. Acidemic NHE8-null mice had an increase in brush-border membrane vesicle NHE3 protein abundance and NHE activity compared with vehicle-treated mice. Likewise, NHE3-null mice had an increase in NHE8 brush-border membrane protein abundance and NHE activity in response to metabolic acidosis. In conclusion, both NHE3 and NHE8 likely play a role in neonatal acidification.