Identification, Localization and Expression of NHE Isoforms in the Alveolar Epithelial Cells

Na+/H+ exchangers (NHEs), encoded by Solute Carrier 9A (SLC9A) genes in human, are ubiquitous integral membrane ion transporters that mediate the electroneutral exchange of H+ with Na+ or K+. NHEs, found in the kidney and intestine, play a major role in the process of fluid reabsorption together via Na+,K+-ATPase pump and Na+ channels. Nevertheless, the expression pattern of NHE in the lung and its role in alveolar fluid homeostasis has not been addressed. Therefore, we aimed to examine the expression of NHE specific isoforms in alveolar epithelium cells (AECs), and assess their role in congestive heart failure. Three NHE isoforms were identified in AEC and A549 cell line, at the level of protein and mRNA; NHE1, NHE2 and mainly NHE8, the latter was shown to be localized in the apical membrane of AEC. Treating A549 cells with angiotensin (Ang) II for 1 and 3 hours displayed a significant reduction in NHE8 protein abundance and to lesser extent at 5 hours; however, there was no effect at 24 hours. Moreover, A549 treated overnight with Ang II downregulated NHE8 protein abundance. CHF rats held for 1 week had increased abundance of NHE8 compared to sham operated rats. However, lower abundance of NHE8 was observed in CHF rats held for 4 weeks. Herein we show, for the first time, the expression of a novel NHE isoform by AEC, namely NHE8. Besides being negatively affected by Ang II, NHE8 protein levels were distinctly affected in CHF rats, which may be related to CHF severity.