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Na+/H+ Exchanger 8 Regulates Alveolar Active Sodium Transport in Heart Failure
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A2255 - Na+/H+ Exchanger 8 Regulates Alveolar Active Sodium Transport in Heart Failure
Author Block: Z. S. Azzam1, S. Kinaneh2, R. M. Ismael-Badarneh2, E. Khoury2, Y. Kinaneh2, J. Khoury1, Z. Abassi2; 1Internal Medicine B, Rambam Health Care Campus, Haifa, Israel, 2Department of Physiology and Biophysics, Bruce Rappaport Faculty of Medicine, Technion, Haifa, Israel.
Background: 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+. Notably, NHEs together with Na+,K+-ATPase pump and Na+ channels contribute to the process of fluid reabsorption in the kidney and intestine. To date, nine isoforms (NHE1-NHE9) have been identified within the mammalian NHE family. NHEs consist of isoforms that occur primarily in the plasma membrane. Notably, the role of the sodium pump and channels is well established in alveolar active sodium transport and lung liquid clearance. Nevertheless, the expression pattern of NHE in the lung, and its role in alveolar fluid homeostasis has not been addressed yet. Therefore, we aimed in this study to examine the expression pattern of NHE specific isoforms in alveolar epithelium cells (AEC), and explore their role in AEC in sham and congestive heart failure (CHF) rats. Methods: The expression of NHE isoforms was assessed in AEC and A549 cells at the mRNA and protein levels. CHF was induced by using the aorto-caval fistula model. Results: By using western blotting, quantitative PCR (qPCR) and immunofluorescence staining, three NHE isoforms were identified in AEC and A549 cells; NHE1, NHE2 and mainly NHE8. By using confocal microscopy, we demonstrated that NHE8 is localized in the apical membrane of AECI. Notably, a strong membrane expression of NHE8 was also observed in the interstitial macrophages. One week following the induction of CHF, the immunoreactive levels of NHE8 was increased by two folds as compared to sham operated rats. Treating A549 cells with angiotensin II (10-8M) for 1 and 3 hours displayed a significant reduction in pulmonary NHE8 protein abundance and to lesser extent at 5 hours. Conclusions: We herein report the expression of a novel NHE isoform by AEC, namely NHE8. While CHF upregulates pulmonary NHE8 expression, Ang II exerted a negative feedback on this exchanger. Further experiments are required in order to explore the mechanisms underlying this phenomenon.
Author Block: Z. S. Azzam1, S. Kinaneh2, R. M. Ismael-Badarneh2, E. Khoury2, Y. Kinaneh2, J. Khoury1, Z. Abassi2; 1Internal Medicine B, Rambam Health Care Campus, Haifa, Israel, 2Department of Physiology and Biophysics, Bruce Rappaport Faculty of Medicine, Technion, Haifa, Israel.
Background: 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+. Notably, NHEs together with Na+,K+-ATPase pump and Na+ channels contribute to the process of fluid reabsorption in the kidney and intestine. To date, nine isoforms (NHE1-NHE9) have been identified within the mammalian NHE family. NHEs consist of isoforms that occur primarily in the plasma membrane. Notably, the role of the sodium pump and channels is well established in alveolar active sodium transport and lung liquid clearance. Nevertheless, the expression pattern of NHE in the lung, and its role in alveolar fluid homeostasis has not been addressed yet. Therefore, we aimed in this study to examine the expression pattern of NHE specific isoforms in alveolar epithelium cells (AEC), and explore their role in AEC in sham and congestive heart failure (CHF) rats. Methods: The expression of NHE isoforms was assessed in AEC and A549 cells at the mRNA and protein levels. CHF was induced by using the aorto-caval fistula model. Results: By using western blotting, quantitative PCR (qPCR) and immunofluorescence staining, three NHE isoforms were identified in AEC and A549 cells; NHE1, NHE2 and mainly NHE8. By using confocal microscopy, we demonstrated that NHE8 is localized in the apical membrane of AECI. Notably, a strong membrane expression of NHE8 was also observed in the interstitial macrophages. One week following the induction of CHF, the immunoreactive levels of NHE8 was increased by two folds as compared to sham operated rats. Treating A549 cells with angiotensin II (10-8M) for 1 and 3 hours displayed a significant reduction in pulmonary NHE8 protein abundance and to lesser extent at 5 hours. Conclusions: We herein report the expression of a novel NHE isoform by AEC, namely NHE8. While CHF upregulates pulmonary NHE8 expression, Ang II exerted a negative feedback on this exchanger. Further experiments are required in order to explore the mechanisms underlying this phenomenon.
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